Skip to main content

Clinical Pharmacokinetics of Antiepileptic Drugs

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 74))

Abstract

Among the various hydantoin compounds which have been tested for anticonvulsant activity in man, phenytoin is by far the most widely prescribed. Phenytoin is normally given orally, although parenteral administration may be occasionally used. Its pharmacokinetics has been studied extensively.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abel JG, Sellers EM, Naranjo CA, Shaw J, Kadar D, Romach MK (1979) Inter- and in- trasubject variation in diazepam free fraction. Clin Pharmacol Ther 26:247–255

    PubMed  CAS  Google Scholar 

  • Abernethy DR, Greenblatt DJ (1981) Metabolite-parent drug interaction study: desmethyl-diazepam effect in diazepam kinetics. Clin Pharmacol Ther 29: 230–231

    Google Scholar 

  • Ackermann E, Richter K (1977) Diazepam metabolism in human foetal and adult liver. Eur J Clin Pharmacol 11: 43–49

    PubMed  CAS  Google Scholar 

  • Agurell S, Berlin A, Ferngren H, Hellstrom B (1975) Plasma levels of diazepam after parenteral and rectal administration in children. Epilepsia 16: 277–283

    PubMed  CAS  Google Scholar 

  • Albert KS, Sakmar E, Hallmark MR, Weidler DJ, Wagner JG (1974) Bioavailability of diphenylhydantoin. Clin Pharmacol Ther 16: 727–735

    PubMed  CAS  Google Scholar 

  • Alexander FW (1979) Sodium valproate and pregnancy. Arch Dis Child 54: 240

    PubMed  CAS  Google Scholar 

  • Alvarez N, Hartford E, Cavalleri E (1981) Low blood levels of phenobarbital due to poor gastrointestinal solubility of phenobarbital tablets. Ann Neurol 9: 305–310

    Google Scholar 

  • Alvin J, McHorse TS, Hoyumpa A, Bush MT, Schenker S (1975) The effect of liver disease in man on the disposition of phenobarbital. J Pharmacol Exp Ther 192: 224–235

    PubMed  CAS  Google Scholar 

  • Anavekar SN, Saunders RH, Wardell WM, Shoulson I, Emmings FG, Cook CE, Gringeri AJ (1979) Parotid and whole saliva in the prediction of serum total and free phenytoin concentrations. Clin Pharmacol Ther 24: 629–637

    Google Scholar 

  • Andoh B, Idle JR, Sloan TP, Smith RL, Woolhouse N (1980) Inter-ethnic and inter-phenotype differences among Ghanaians and Caucasians in the metabolic hydroxylation of phenytoin. Br J Clin Pharmacol 9: 282–283 P

    Google Scholar 

  • Andresen BD, Davis FT, Templeton JL (1976) Synthesis and characterization of alphaphenyl gamma butyrolactone, a metabolite of glutethimide, phenobarbital and primidone, in human urine. Res Commun Chem Pathol Pharmacol 15: 21–30

    PubMed  CAS  Google Scholar 

  • Andreasen PB, Hendel J, Greisen G, Hvidberg EF (1976) Pharmacokinetics of diazepam in disordered liver function. Eur J Clin Pharmacol 10: 115–120

    PubMed  CAS  Google Scholar 

  • Anttila M, Kahela P, Panelius M, Yriana T, Tikkanen R, Aaltonen R (1979) Comparative bioavailability of two commercial preparations of carbamazepine tablets. Eur J Clin Pharmacol 15: 421–425

    PubMed  CAS  Google Scholar 

  • Arnold K, Gerber N (1970) The rate of decline of diphenylhydantoin in human plasma. Clin Pharmacol Ther 11: 121–134

    PubMed  CAS  Google Scholar 

  • Ashley J J, Levy G (1972) Inhibition of diphenylhydantoin elimination by its major metabolite. Res Commun Chem Pathol Pharmacol 4: 297–306

    PubMed  CAS  Google Scholar 

  • Ashley JJ, Levy G (1973) Kinetics of diphenylhydantoin elimination in rats. J Pharmacokinet Biopharm 1: 99–102

    PubMed  CAS  Google Scholar 

  • Atkinson AJ Jr, Mac Gee J, Strong J, Garteiz D, Gaffney TE (1970) Identification of 5-toxicity. Clin Pharmacol Ther 14: 521–528

    Google Scholar 

  • Atinson AJ Jr, Mac Gee J, Strong J, Garteiz D, Gaffney TE (1970) Identification of 5-meta-hydroxyphenyl-5-phenylhydantoin as a metabolite of diphenylhydantoin. Biochem Pharmacol 19: 2483–2491

    Google Scholar 

  • Ayers GI, Burnett D (1977) Drug formulations and salivary phenytoin measurements. Lancet 1: 656–657

    PubMed  CAS  Google Scholar 

  • Bailey DN, Jatlow PI (1972) Clinical analysis of massive crystalluria following primidone overdose. Am J Clin Pathol 58: 583–589

    PubMed  CAS  Google Scholar 

  • Barron SJ, Darcey BA, Booker HE (1974) Metabolism and kinetics of methsuximide in man. Neurology 24: 386

    Google Scholar 

  • Bartels H, Günther E, Wallis S (1979) Flow-dependent salivary primidone levels in epileptic children. Epilepsia 20: 431–436

    PubMed  CAS  Google Scholar 

  • Barth N, Alvan G, Borga O, Sjoqvist F (1976) Two–fold interindividual variation in plasma protein binding of phenytoin in patients with epilepsy. Clin Pharmacokinet 1: 444–452

    PubMed  CAS  Google Scholar 

  • Battino D, Bossi L, Croci D, Cusi C, Gomeni C, Moise A, Spina S (1980) Plasma levels of primidone and phenobarbital in children and adults: influence of age and associated therapy. Acta Neurol Scan [Suppl] 62: 101

    Google Scholar 

  • Baumel IP, Gallagher BB, Mattson RH (1972) Phenylethylmalonamide ( PEMA) An important metabolite of primidone. Arch Neurol 27: 34–41

    Google Scholar 

  • Berlin A, Dahlström H (1975) Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral dose and intravenous doses and by repeated oral administration. Eur J Clin Pharmacol 9: 155–159

    PubMed  CAS  Google Scholar 

  • Berlin A, Siwers B, Agurell S, Hiort A, Sjöqvist F, Ström S (1975) Determination of bioavailability of diazepam in various formulations from steady-state plasma concentration data. Clin Pharmacol Ther 13: 733–744

    Google Scholar 

  • Berman PH (1976) Management of seizure disorders with anticonvulsant drugs: current concepts. Pediatr Clin North Am 23: 443–459

    PubMed  CAS  Google Scholar 

  • Bertilsson L (1978) Clinical pharmacokinetics of carbamazepine. Clin Pharmacokinet 3: 128–143

    PubMed  CAS  Google Scholar 

  • Bertilsson L, Hojer B, Tybring G, Osterloh J, Rane A (1980) Autoinduction of carbamazepine metabolism in children examined by a stable isotope technique. Clin Pharmacol Ther 27: 83–88

    PubMed  CAS  Google Scholar 

  • Blain PG, Mucklow JC, Bacon CJ, Rawlins MD (1981) Pharmacokinetics of phenytoin in children. Br J Clin Pharmacol 12: 659–662

    PubMed  CAS  Google Scholar 

  • Blashke TF, Meffin PJ, Melmon KL, Rowland M (1975) Influence of acute viral hepatitis on phenytoin kinetics and protein binding. Clin Pharmacol Ther 17: 685–691

    Google Scholar 

  • Bochner F, Hooper WD, Tyrer JH, Eadie MJ (1972) Factors involved in an outbreak of phenytoin intoxication. J Neurol Sci 16: 481–487

    PubMed  CAS  Google Scholar 

  • Bochner F, Hooper WD, Sutherland JM, Eadie MJ, Tyrer JH (1974) Diphenylhydantoin concentrations in saliva. Arch Neurol 3: 57–59

    Google Scholar 

  • Booker HE (1972) Trimethadione and other oxazolidinediones. Relation of plasma levels to clinical control. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 403–407

    Google Scholar 

  • Booker HE, Hosokowa K, Burdette RD, Darcey B (1970) A clinical study of serum primidone levels. Epilepsia 11: 395–402

    PubMed  CAS  Google Scholar 

  • Boreus LO, Jailing B, Wallin A (1978) Plasma concentrations of phenobarbital in mother and child after combined prenatal and postnatal administration for prophylaxis of hyperbilirubinemia. J Pediatr 93: 695–698

    PubMed  CAS  Google Scholar 

  • Borga O, Juhlin-Dannfeldt A, Dahlqvist R (1978) Plasma levels and protein binding of phenytoin during exercise in man. The effect of elevated free fatty acids. Pharmacology 16: 37–43

    Google Scholar 

  • Borga O, Hoppel C, Odar-Cederlof I, Garle M (1979) Plasma levels and renal excretion of phenytoin and its metabolites in patients with renal failure. Clin Pharmacol Ther 26: 306–314

    PubMed  CAS  Google Scholar 

  • Borofsky LG, Louis S, Kutt H (1973) Diphenylhydantoin in children. Pharmacology and efficacy. Neurology 23: 967–972

    Google Scholar 

  • Borondy P, Dill WA, Chang T, Buchanan R, Glazko A (1973) Effect of protein binding on the distribution of 5,5-diphenylhydantoin between plasma and red cells. Ann NY Acad Sci 222: 82–87

    Google Scholar 

  • Borst SI, Lookwood CH (1975) Plasma level studies on different brands of sodium diphenylhydantoin ( DPH) and primidone. Int J Clin Pharmacol Biopharm 12: 309–314

    Google Scholar 

  • Boutroy MJ, Royer-Morrot MJ, Legras B, Royer RJ, Vert P, Moreau RM (1980) Pharmacocinetique du phenobarbital chez le nouveaune. In: Mathieu H, Pantonnier G, Olive G (eds) Pharmacologic de developpement, INSERM Seminar vol 89 pp 329–338

    Google Scholar 

  • Bowdle TA, Levy RH, Cutler RE (1979) Effect of carbamazepine on valproic acid kinetics in normal subjects. Clin Pharmacol Ther 26: 629–634

    PubMed  CAS  Google Scholar 

  • Bowdle TA, Patel IH, Levy RH, Wilensky AJ (1980) Valproic acid dosage and plasma protein binding and clearance. Clin Pharmacol Ther 28: 486–492

    PubMed  CAS  Google Scholar 

  • Brachet-Liermain A, Demarquez JL (1977) Pharmacokinetics of dipropyl acetate in infants and young children. Pharm Weekbl [Sci] 112: 293–297

    CAS  Google Scholar 

  • Brachet-Liermain A, Goutieres F, Aicardi J (1975) Absorption of phenobarbital after the intramuscular administration of single doses in infants. J Pediatr 87: 624–626

    PubMed  CAS  Google Scholar 

  • Branch RA, Morgan MH, James J, Read AE (1976) Intravenous administration of diazepam in patients with chronic liver disease. Gut 17: 975–983

    PubMed  CAS  Google Scholar 

  • Brandt R (1976) Passage of diazepam and desmethyldiazepam in breast milk, Arzneimittelforsch 26: 454–457

    PubMed  CAS  Google Scholar 

  • Braun CW, Goldstone JM (1980) Increased clearance of phenytoin as the presenting feature of infectious mononucleosis. Ther Drug Monit 2: 355–357

    PubMed  CAS  Google Scholar 

  • Brewster D, Muir NC (1980) Valproate plasma protein binding in the uremic condition. Clin Pharmacol Ther 27: 76–82

    PubMed  CAS  Google Scholar 

  • Brillman J, Gallagher BB, Mattson RH (1974) Acute primidone intoxication. Arch Neurol 30: 255–258

    PubMed  CAS  Google Scholar 

  • Browne TR, Dreifuss FE, Dynen PR, Goode DJ, Penry JK, Porter RJ, White BG, White PT (1975) Ethosuximide in the treatment of absence (petit mal) seizures. Neurology 25: 515–524

    PubMed  CAS  Google Scholar 

  • Browne TR, Van Langenhove A, Costello CE, Biemann K, Greenblatt DJ (1981) Kinetic equivalence of stable-isotope-labelled and unlabelled phenytoin. Clin Pharmacol Ther 29: 511–515

    PubMed  CAS  Google Scholar 

  • Bruni J, Wang LH, Marbury TC, Lee CS, Wilder BJ (1979) Protein binding of valproic acid in uremic patients. Neurology 30: 557–559

    Google Scholar 

  • Buchanan RA, Fernandez L, Kinkel AW (1969) Absorption and elimination of ethosuximide in children. J Clin Pharmacol 9: 393–398

    CAS  Google Scholar 

  • Buchanan RA, Kinkel AW, Smith TC (1973 a) The absorption and excretion of ethosuximide. Int Clin Pharmacol Ther Toxicol 7: 213–218

    Google Scholar 

  • Buchanan RA, Turner JL, Moyer CF, Heffelflnger JC (1973 b) Single daily dose of diphenylhydantoin in children. J Pediatr 83: 479–483

    Google Scholar 

  • Buchanan RA, Kinkel AW, Turner J, Heffelflnger JC (1976) Ethosuximide dosage regimens. Clin Pharmacol Ther 19: 142–147

    Google Scholar 

  • Butler TC (1955) Metabolic demethylation of 3,5-dimethyl-5-ethyl 2,4-oxazolidinedione (paramethadione, paradione) J Pharmacol Exp Ther 113: 178–185

    Google Scholar 

  • Butler TC (1956 a) The metabolic conversion of 3-methyl-5-ethyl-5-phenylhydantoin (mesantoin) and of 5-ethyl-5-phenylhydantoin (nirvanol) to 5-ethyl-5-(p-hydroxyphenyl)-hydantoin. J Pharmacol Exp Ther 117:160–165

    Google Scholar 

  • Butler TC (1956 a) The metabolic hydroxylation of phenobarbital. J Pharmacol Exp Ther 116:326–336

    Google Scholar 

  • Butler TC (1957) The metabolic conversion of 5-5-diphenylhydantoin to 5-(p-hydroxy-phenyl)-5-phenylhydantoin. J Pharmacol Exp Ther 119: 1–11

    PubMed  CAS  Google Scholar 

  • Butler TC, Waddell WJ (1958) N-Methylated derivatives of barbituric acids, hydantoin and oxazolidinedione used in the treatment of epilepsy. Neurology [Suppl 1] 8: 106–112

    CAS  Google Scholar 

  • Butler TC, Mahaffee C, Waddell WJ (1954) Phenobarbital: studies of elimination, accumulation, tolerance and dosage schedule. J Pharmacol Exp Ther 111: 425–435

    PubMed  CAS  Google Scholar 

  • Cate JC, Tenser R (1975) Acute primidone overdosage with massive crystalluria. Clin Toxicol 8: 385–389

    PubMed  Google Scholar 

  • Cereghino JJ, Brock JT, Van Meter JC, Penry JK, Smith LD, White BG (1975) The efficacy of carbamazepine combinations in epilepsy. Clin Pharmacol Ther 18: 733–741

    PubMed  CAS  Google Scholar 

  • Chamberlin HR, Waddell WJ, Butler TC (1965) A study of the product of demethylation of trimethadione in the control of petit mal epilepsy. Neurology 15: 449–454

    PubMed  CAS  Google Scholar 

  • Chang T, Dill WA, Glazko AJ (1972) Ethosuximide. Absorption, distribution and excretion. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 417–423

    Google Scholar 

  • Chen SS, Perucca E, Lee J-N, Richens A (1982) Serum protein binding and free concentration of phenytoin and phenobarbitone in pregnancy. Br J Clin Pharmacol 4: 551–554

    Google Scholar 

  • Christiansen J, Dam M (1973) Influence of phenobarbital and diphenylhydantoin on plasma carbamazepine levels in patients with epilepsy. Acta Neurol Scand 49: 543–546

    PubMed  CAS  Google Scholar 

  • Chun AHC, Hoffman DJ, Friedmann N, Carrigan PJ (1980) Bioavailability of valproic acid under fasting/nonfasting regimens. J Clin Pharmacol 20: 30–36

    PubMed  CAS  Google Scholar 

  • Cloyd JC, Miller KW, Leppik IE (1981) Primidone kinetics: effects of concurrent drugs and duration of therapy. Clin Pharmacol Ther 29: 402–407

    PubMed  CAS  Google Scholar 

  • Cocks DA, Critchley EMR, Hayward HW, Owen V, Mawer GE, Woodcock BG (1975) Control of epilepsy with a single daily dose of phenytoin sodium. Br J Clin Pharmacol 2: 449–553

    PubMed  CAS  Google Scholar 

  • Cossum PA, Roberts MS (1981) Availability of isosorbide dinitrate, diazepam and chlormethiazole from i.v. delivery systems. Eur J Clin Pharmacol 19: 181–185

    PubMed  CAS  Google Scholar 

  • Cotter LM, Eadie MJ, Hooper WD, Lander CM, Smith GA, Tyrer JH (1977) The pharmacokinetics of carbamazepine. Eur J Clin Pharmacol 12: 451–456

    PubMed  CAS  Google Scholar 

  • Cottrell PR, Street JM, Berry DJ, Schafer H, Pisani F, Perucca E, Richens A (1982) Pharmacokinetics of phenylethylmalonamide ( PEMA) in normal subjects and in patients treated with antiepileptic drugs. Epilepsia 23: 307–313

    Google Scholar 

  • Cramer J A, Mattson RH (1979) Valproic acid: in vitro plasma protein binding and interaction with phenytoin. Ther Drug Monit 1: 105–116

    PubMed  CAS  Google Scholar 

  • Dam M, Christiansen J, Munck O, Mygind KI (1979) Antiepileptic drugs: metabolism in pregnancy. Clin Pharmacokinet 4: 53

    PubMed  CAS  Google Scholar 

  • Dam M, Christiansen J, Christiansen CB, Helles A, Jaegerskou A, Schmiegelow M (1981) Carbamazepine: a clinical biopharmaceutical study. Eur J Clin Pharmacol 20: 59–64

    PubMed  CAS  Google Scholar 

  • Dasberg HH, Van Der Kleijn E, Guelen PJR, Van Praag HM (1974) Plasma concentrations of diazepam and its metabolite N-desmethyldiazepam in relation to anxiolytic effect. Clin Pharmacol Ther 15: 473–483

    PubMed  CAS  Google Scholar 

  • Dhillon S, Richens A (1981a) Bioavailability of rectally administered diazepam in adult epileptic patients. Br J Clin Pharmacol 11: 437–438 P

    Google Scholar 

  • Dhillon S, Richens A (1981 b) Pharmacokinetics of diazepam in epileptic patients and normal volunteers following intravenous administration. Br J Clin Pharmacol 12: 841–844

    Google Scholar 

  • Diamond S, Levy L (1963) Metabolic studies on a new anti-epileptic drug: Riker 594. Curr Ther Res 5: 325–330

    Google Scholar 

  • Dickinson RG, Harland RC, Lynn RK, Smith WB, Gerber N (1979) Transmission of valproic acid (Depakene) across the placenta: half-life of the drug in mother and baby. J Pediatr 94: 832–835

    PubMed  CAS  Google Scholar 

  • Di Gregorio GJ, Peraino AJ, Ruch E (1978) Diazepam concentrations in parotid saliva, mixed saliva and plasma. Clin Pharmacol Ther 24: 720–725

    Google Scholar 

  • Di Salle E, Pacifici GM, Morselli PL (1974) Studies on plasma protein binding of carbamazepine. Pharmacol Res Commun 6: 193–202

    PubMed  Google Scholar 

  • Divoll-Allen MRN, Greenblatt DJ (1981) Absolute bioavailability of oral and intramuscular diazepam. Clin Pharmacol Ther 29: 240–241

    Google Scholar 

  • Dixon R, Crews T (1978) Diazepam: determination in micro samples of blood, plasma, and saliva by radioimmunoassay. J Anal Toxicol 2: 210–213

    CAS  Google Scholar 

  • Dodson EW (1980) Phenytoin elimination in childhood: effect of concentration-dependent kinetics. Neurology 30: 196–199

    PubMed  CAS  Google Scholar 

  • Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S (1975) Serum clonazepam concentrations in children with absence seizures. Neurology, 25: 255–258

    PubMed  CAS  Google Scholar 

  • Driessen O, Van Der Velde E, Hoppener R (1980) Practical and theoretical aspects of phenytoin administration. II Prediction of plasma concentration. Eur Neurol 19: 103–114

    Google Scholar 

  • Dudley KH, Bius DL, Butler TC (1970) Metabolic fates of 3-ethyl-5-phenylhydantoin (ethotoin, Peganone®), 3-methyl-5-phenyl-hydantoin and 5-phenylhydantoin. J Pharmacol Exp Ther 175: 27–37

    PubMed  CAS  Google Scholar 

  • Eadie MJ (1976) Plasma level monitoring of anticonvulsants. Clin Pharmacokinet 1: 52–66

    PubMed  CAS  Google Scholar 

  • Eadie MJ, Tyrer JH (1980) Anticonvulsant therapy, Churchill-Livingstone, Edinburgh

    Google Scholar 

  • Eadie MJ, Tyrer JH, Bochner F, Hooper WD (1976) The elimination of phenytoin in man. Clin Exp Pharmacol Physiol 3: 217–224

    PubMed  CAS  Google Scholar 

  • Eadie MJ, Lander CM, Hooper WD, Tyrer JH (1977 a) Factors influencing plasma phenobarbitone levels in epileptic patients. Br J Clin Pharmacol 4: 541–547

    Google Scholar 

  • Eadie MJ, Tyrer JH, Smith GA, McKauge L (1977 b) Pharmacokinetics of drugs used for petit mal absence epilepsy. Clin Exp Neurol 14: 172–183

    Google Scholar 

  • Eadie MJ, Bochner F, Hooper WD, Tyrer JH (1978) Preliminary observations on the pharmacokinetics of methylphenobarbitone. Clin Exp Neurol 15: 131–144

    PubMed  CAS  Google Scholar 

  • Ehrnebo M, Odar-Cederlof I (1975) The binding of amobarbital, pentobarbital and diphe-nylhydantoin to blood cells and plasma proteins in healthy volunteers and uremic patients. Eur J Clin Pharmacol 8: 445–453

    PubMed  CAS  Google Scholar 

  • Ehrnebo M, Agurell S, Jailing B, Boreus LO (1971) Age differences in drug binding by plasma proteins: studies on human foetuses, neonates and adults. Eur J Clin Pharmacol 3: 189–193

    PubMed  CAS  Google Scholar 

  • Eichelbaum M, Ekbom K, Bertilsson L, Ringberger VA, Rane A (1975) Plasma kinetics of carbamazepine and its epoxide in man during single and multiple dosing. Eur J Clin Pharmacol 8: 337–341

    PubMed  CAS  Google Scholar 

  • Eichelbaum M, Bertilsson L, Lund L, Palmer L, Sjoqvist F (1976) Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during carbamazepine therapy in epileptic patients. Eur J Clin Pharmacol 9: 417–421

    CAS  Google Scholar 

  • Eichelbaum M, Kothe KW, Hoffmann F, Von Unruh GE (1979) Kinetics and metabolism of carbamazepine during combined antiepileptic therapy. Clin Pharmacol Ther 26: 366–371

    PubMed  CAS  Google Scholar 

  • Elfstrom J (1977) Plasma protein binding of phenytoin after cholecystectomy and

    Google Scholar 

  • neurosurgical operations. Acta Neurol Scand 55:455–464

    Google Scholar 

  • Erkkola R, Kanto J (1972) Diazepam and breast feeding. Lancet 1: 1235–1236

    PubMed  CAS  Google Scholar 

  • Erkkola R, Kanto J, Sellman R (1974) Diazepam in early human pregnancy. Acta Obstet Gynaecol, Scand 53: 135–138

    Google Scholar 

  • Eschenof VE (1973) Untersuchungen iiber das Schicksal des Antikonvulsivums Clonazepam im Organismus der Ratte, des Hundes und des Menschen. Arzneimittelforsch 23: 390–400

    Google Scholar 

  • Espir MLE, Benton P, Will E, Hayes MJ, Walker G (1976) Sodium valproate (Epilim)-some clinical and pharmacological aspects. In: Legg NJ (ed) Clinical and pharmacological aspects of sodium valproate (Epilim) in the treatment of epilepsy. MCS Consultants, Tunbridge Wells, pp 145–151

    Google Scholar 

  • Faigle JW, Feldmann KF (1975) Pharmacokinetic data of carbamazepine and its major metabolites in man. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi M, Sherwin AS (eds) Clinical pharmacology of anti-epileptic drugs. Springer, Berlin Heidelberg New York, pp 159–165

    Google Scholar 

  • Fredholm BB, Rane A, Persson B (1975) Diphenylhydantoin binding to proteins in plasma and its dependence on free fatty acids and bilirubin concentration in dogs and newborn infants. Pediatr Res 9: 26–30

    CAS  Google Scholar 

  • Frey HH (1969) Determination of the anticonvulsant potency of unmetabolized trimethadione. Acta Pharmacol Toxicol 27: 295–300

    CAS  Google Scholar 

  • Frigerio A, Morselli PL (1975) Carbamazepine: biotransformation. In: Penry JK, Daly DD (eds) Advances in neurology, vol II. Raven, New York pp 275–280

    Google Scholar 

  • Frigo GM, Lecchini S, Gatti G, Perucca E, Crema A (1979) Modification of phenytoin clearance by valproic acid in normal subjects. Br J Clin Pharmacol 8: 553–556

    PubMed  CAS  Google Scholar 

  • Friis ML, Christiansen J, Hvidberg EF (1978) Brain concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients. Eur J Clin Pharmacol 14: 47–51

    PubMed  CAS  Google Scholar 

  • Galeazzi RL, Egli M, Wad N (1979) Pharmacokinetics of phenylethylacetylurea (pheneturide) an old antiepileptic drug. J Pharmacokinet Biopharm 7: 453–462

    PubMed  CAS  Google Scholar 

  • Gallagher BB, Baumel IP (1972) Primidone. Biotransformation. In: Woodbury DM, Penry JK, Schmidt RP (eds). Antiepileptic drugs, Raven, New York, pp 361–366

    Google Scholar 

  • Gallagher BB, Baumel IP, Mattson RH (1972) Metabolic disposition of primidone and its metabolites in epileptic subjects after single and repeated administration. Neurology 22: 1186–1192

    PubMed  CAS  Google Scholar 

  • Gamble J AS, Dundee JW, Assaf RAE (1975) Plasma diazepam levels after single oral and intramuscular administration. Anaesthesia 30: 164–169

    PubMed  CAS  Google Scholar 

  • Garrettson LK, Dayton PG (1970) Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clin Pharmacol Ther 11: 674–679

    PubMed  CAS  Google Scholar 

  • Garrettson LK, Jusko WJ (1975) Diphenylhydantoin elimination kinetics in overdosed children. Clin Pharmacol Ther 17: 481–491

    PubMed  CAS  Google Scholar 

  • Garrettson LK, Kim OK (1970) Apparent saturation of diphenylhydantoin metabolism in children. Pediat Res 4: 455

    Google Scholar 

  • Gatti G, Perucca E, Caravaggi M, Poloni M, Frigo GM, Crema A (1977) Pharmacokinetics of phenytoin following intravenous administration in epileptic patients. Farmaco (Prat) 32: 470–474

    CAS  Google Scholar 

  • Gerardin A, Hirz J (1976) The quantitative assay of carbamazepine in biological material and its application to basic pharmacokinetic studies. In: Birkmayer H (ed) Epileptic seizures, behaviour, pain. Huber, Berne, pp 151–164

    Google Scholar 

  • Gerardin AP, Abadie FV, Campestrini J A, Theobald W (1976) Pharmacokinetics of carbamazepine in normal humans after single and repeated oral doses. J Pharmacokinet Biopharm 4: 521–535

    CAS  Google Scholar 

  • Gerber N, Weller WL, Lynn R, Rangno RE, Sweetman BJ, Bush MT (1971) Study of dose-dependent metabolism of 5,5-diphenylhydantoin in the rat using new methodology for isolation and quantitation of metabolites in vivo and in vitro. J Pharmacol Exp Ther 178: 567–579

    PubMed  CAS  Google Scholar 

  • Gerber N, Thompson RM, Smith RG, Lynn RK (1979) Evidence for the epoxidediol pathway in the biotransformation of mephenytoin. Epilepsia 20: 287–294

    PubMed  CAS  Google Scholar 

  • Giacomini K, Giacomini J, Blaschke T (1980) Heparin decreases plasma protein binding of drugs. Clin Pharmacol Ther 27: 256

    Google Scholar 

  • Giles HH, Zilm DH, Frecker RC, Macleod SM, Sellers EM (1977) Saliva and plasma concentrations of diazepam after a single oral dose. Br J Clin Pharmacol 4: 711–712

    CAS  Google Scholar 

  • Glazko AJ (1973) Diphenylhydantoin metabolism. A prospective review. Drug Metab Dispos 1: 711–714

    PubMed  CAS  Google Scholar 

  • Glazko AJ (1975) Antiepileptic drugs: biotransformation, metabolism and serum half-life. Epilepsia 16: 367–391

    PubMed  CAS  Google Scholar 

  • Glazko AJ, Dill WA (1972) Other succinimides. Methsuximide and phensuximide. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 455–464

    Google Scholar 

  • Glazko AJ, Dill WA, Wolf LM, Miller CA (1954) The determination and physiological disposition of Milontin ( N-methyl-α-phenylsuccinimide ). J Pharmacol Exp Ther 111: 413–424

    Google Scholar 

  • Glazko A J, Chang T, Baukema J, Dill WA, Goulet JR, Buchanan RA (1969) Metabolic disposition of diphenylhydantoin in normal human subjects following intravenous administration. Clin Pharmacol Ther 10: 498–504

    PubMed  CAS  Google Scholar 

  • Goldberg MA, Crandall PH (1978) Human brain binding of phenytoin. Neurology 28: 881–885

    PubMed  CAS  Google Scholar 

  • Goldberg MA, Gal J, Cho AK, Jenden DJ (1979) Metabolism of dimethoxymethylphenobarbital ( Eterobarb) in patients with epilepsy. Ann Neurol 5: 121–126

    Google Scholar 

  • Goulet JR, Kinkel AW, Smith TC (1976) Metabolism of ethosuximide. Clin Pharmacol Ther 20: 213–218

    PubMed  CAS  Google Scholar 

  • Gram L, Flachs H, Wurtz-Jorgensen A, Parnas J, Andersen B (1979) Sodium valproate, serum level and clinical effect in epilepsy: a controlled study. Epilepsia 20: 303–312

    PubMed  CAS  Google Scholar 

  • Green JR, Kupferberg HJ (1972) Sulfonamides and derivatives Sulthiame. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 477–485

    Google Scholar 

  • Green JR, Troupin AS, Halpern LM, Friel P, Kanarek P (1974) Sulthiame: evaluation as an anticonvulsant. Epilepsia 15: 329–349

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Maclaughlin DS, Harmatz JS, Shader RI (1978 a) Diazepam absorption: effects of antacids and food. Clin Pharmacol Ther 24: 600–609

    Google Scholar 

  • Greenblatt DJ, Divoll-Allen M, Harmatz JS, Shader RI (1980) Diazepam disposition determinants. Clin Pharmacol Ther 27: 301–312

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Laughren TP, Allen MD, Harmatz JS, Shader RI (1981) Plasma diazepam and desmethyl-diazepam concentrations during long-term diazepam therapy. Br J Clin Pharmacol 11: 35–40

    PubMed  CAS  Google Scholar 

  • Griffiths A, Hebdige S, Perucca E, Richens A (1980) Quality control in drug measurements. Ther Drug Monit 2: 51–60

    PubMed  CAS  Google Scholar 

  • Gruska H, Beyer KH, Kubicki S, Schneider H (1971) Klinik, Toxikologie und Therapie eine schweren Carbamazepine-Vergiftung. Arch Toxicol 27: 193–203

    Google Scholar 

  • Guelen PJM, Deimann LGJ (1980) Influence of plasma lipids on the protein binding of diphenylhydantoin and its clinical significance. In: Johannessen SI, Morselli PL, Pippenger CE, Richens A, Schmidt D, Meinardi H (eds) Antiepileptic therapy: advances in drug monitoring. Raven, New York, pp 185–192

    Google Scholar 

  • Gugler R, Azarnoff DL (1976) Drug protein binding and the nephrotic syndrome. Clin Pharmacokinet 1: 25–35

    PubMed  CAS  Google Scholar 

  • Gugler R, Muller G (1978) Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease. Br J Clin Pharmacol 5: 441–446

    PubMed  CAS  Google Scholar 

  • Gugler R, Von Unruh GE (1981) Clinical pharmacokinetics of valproic acid. Clin Pharmacokinet 5: 67–83

    Google Scholar 

  • Gugler R, Shoeman DW, Azarnoff DL (1974) Effect of in vivo elevation of free fatty acids on protein binding of drugs. Pharmacology 12:160 Gugler R, Manion CV, Azarnoff DL (1976) Phenytoin: pharmacokinetics and bioavailability. Clin Pharmacol Ther 19: 135–142

    Google Scholar 

  • Gugler R, Schell A, Eichelbaum M, Froscher W, Schultz HV (1977) Disposition of valproic acid in man. Eur J Clin Pharmacol 12: 125–132

    PubMed  CAS  Google Scholar 

  • Haidukewych D, Rodin EA (1980) Monitoring 2-ethyl-3-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone. Clin Chem 26: 1537–1539

    PubMed  CAS  Google Scholar 

  • Hallstrom C, Lader MH, Curry SH (1980) Diazepam and its N-desmethyldiazepam concentrations in saliva, plasma and CSF. Br J Clin Pharmacol 9: 333–339

    PubMed  CAS  Google Scholar 

  • Hansen SE, Feldberg L (1964) Absorption and elimination of Zarontin. Dan Med Bull 11: 54–55

    PubMed  CAS  Google Scholar 

  • Harvey DJ, Glazener L, Stratton C, Nowlin J, Hill RM, Horning MG (1972) Detection of a 5-(3,4-dihydroxy-l,5-cyclo-hexadiene-l-yl)-metabolite of phenobarbital and mephobarbital in rat, guinea pig and human. Res Commun Chem Pathol Pharmacol 3: 557–566

    PubMed  CAS  Google Scholar 

  • Hayes MJ, Langman MJS, Short AH (1975) Changes in drug metabolism with increasing age. II. Phenytoin clearance and protein binding. Br J Clin Pharmacol 2: 73–79

    Google Scholar 

  • Heimann G, Gladtke E (1977) Parmacokinetics of phenobarbital in childhood. Eur J Clin Pharmacol 12: 305–310

    PubMed  CAS  Google Scholar 

  • Heimann G, Neuwald F, Gladtke E (1978) Die rektale Absorption von Phenobarbital bei Kindern unter dem EinfluB verschiedener Vehikel. Arzneimittelforsch 28: 1023–1027

    PubMed  CAS  Google Scholar 

  • Heipertz R, Guthoff A, Bernhardt W (1979) Primidone metabolism in renal insufficiency and acute intoxication. J Neurol 221: 101–104

    PubMed  CAS  Google Scholar 

  • Hendel J (1975) Cumulation in the cerebrospinal fluid of the N–desmethyl metabolite after long-term treatment with diazepam in man. Acta Pharmacol Toxicol 37: 17–22

    CAS  Google Scholar 

  • Hillestad L, Hansen T, Melsom H ( 1974 a) Diazepam metabolism in normal man. II. Serum concentration and clinical effect after oral administration and cumulation. Clin Pharmacol Ther 16: 485–489

    Google Scholar 

  • Hillestad L, Hansen T, Melsom H, Driveness A ( 1974 b) Diazepam metabolism in normal man. I. Serum concentrations and clinical effects after intravenous, intramuscular and oral administration. Clin Pharmacol Ther 16: 479–484

    Google Scholar 

  • Hoffman DJ, Chun AHC (1975) Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose. J Pharm Sci 64: 1702–1703

    PubMed  CAS  Google Scholar 

  • Hooper WD, Eadie MJ, Tyrer JH (1973) Plasma diphenylhydantoin levels in Australian children. Aust NZ J Med 4: 456–461

    Google Scholar 

  • Hooper W, Bochner F, Eadie MJ, Tyrer JH ( 1974 a) Plasma protein binding of diphenylhydantoin. Effects of sex hormones, renal and hepatic disease. Clin Pharmacol Ther 15: 276–282

    Google Scholar 

  • Hooper WD, Dubetz DK, Eadie MJ, Tyrer JH ( 1974 b) Preliminary observations on the clinical pharmacology of carbamazepine ( Tegretol ). Proc Aust Ass Neurol 11: 189–198

    Google Scholar 

  • Hooper WD, Dubetz DK, Bochner F, Cother LM, Smith GA, Eadie MJ, Tyrer JH (1975)

    Google Scholar 

  • Plasma protein binding of carbamazepine. Clin Pharmacol Ther 17:433–440

    Google Scholar 

  • Hooper WD, Kunze HE, Eadie MJ (1981) Pharmacokinetics and bioavailability of methylphenobarbital in man. Ther Drug Monitor 3: 39–44

    CAS  Google Scholar 

  • Hoppel C, Garle M, Rane A, Sjdqvist F (1977) Plasma concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin in phenytoin treated patients. Clin Pharmacol Ther 21: 294–300

    PubMed  CAS  Google Scholar 

  • Hoppener RJ, Kuyer A, Meijer JWA, Huisman J (1980) Correlation between daily fluctuations of carbamazepine serum levels and intermittent side effects. Epilepsia 21: 341–350

    PubMed  CAS  Google Scholar 

  • Horning MG, Stratton C, Wilson A, Horning EC, Hill RM (1971) Detection of 5-(3,4-di-hydroxy-l,5-cyclohexadiene-l-yl)-5-phenylhydantoin ( Dilantin) in the newborn human. Anal Lett 4: 537–545

    Google Scholar 

  • Horning MG, Butler C, Harvey DJ, Hill RM, Zion TE (1973) Metabolism of N,2-di-methyl-2-phenylsuccinimide (methsuximide) by the epoxide diol pathway in rat, guinea pig and human. Res Commun Chem Pathol Pharmacol 6: 565–578

    PubMed  CAS  Google Scholar 

  • Horning MG, Nowlin J, Butler CM, Letratanangkoon K, Sommer K, Hill RM (1975) Clinical applications of gas-chromatograph/mass spectrometer/computer systems. Clin Chem 21: 1282–1287

    PubMed  CAS  Google Scholar 

  • Houghton GW, Richens A (1974 a) Rate of elimination of tracer doses of phenytoin at different steady-state serum concentrations in epileptic patients. Br J Clin Pharmacol 1: 155–161

    Google Scholar 

  • Houghton GW, Richens A (1974 b) Phenytoin intoxication induced by sulthiame in epileptic patients. J Neurol Neurosurg Psych 37: 275–281

    Google Scholar 

  • Houghton GW, Richens A, Toseland PA, Davidson S, Falconer MA (1975 a) Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients. Eur J Clin Pharmacol 9: 73–78

    Google Scholar 

  • Houghton GW, Richens A, Leighton M (1975 b) Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients. Br J Clin Pharmacol 2: 251–256

    Google Scholar 

  • Huang CY, McLeod JG, Sampson D, Hensley WJ (1974) Clonazepam in the treatment of epilepsy. Med J Aust 2: 5–8

    PubMed  CAS  Google Scholar 

  • Irvine-Meek JM, Hall KW, Otten NH, Leroux M, Budnik M, Seshia SS (1981) Pharmacokinetic study of valproic acid in a neonate. Clin Pharmacol Ther 29: 253–254

    Google Scholar 

  • Jailing B (1974) Plasma and cerebrospinal fluid concentrations of phenobarbital in infants given single doses. Dev Med Child Neurol 16: 785–793

    Google Scholar 

  • Jailing B, Boreus LO, Rane A, Sjoqvist F (1970) Plasma concentrations of diphenylhydantoin in young infants. Pharmacologia Clinica 2: 200–202

    Google Scholar 

  • Jailing B, Boreus LO, Kallberg N, Agurell S (1973) Disappearance of circulating prenatally administered phenobarbital. Eur J Clin Pharmacol 6: 234–238

    Google Scholar 

  • Jensen BN (1962) Trimethadione in serum of patients with petit mal epilepsy. Dan Med Bull 9: 74–79

    PubMed  CAS  Google Scholar 

  • Johannessen SI, Strandjord RE (1972) The concentration of carbamazepine (Tegretol®) in serum and in cerebrospinal fluid in patients with epilepsy. Acta Neurol Scand [Suppl 51] 48: 445–446

    Google Scholar 

  • Johannessen SI, Strandjord RE ( 1975 a) Absorption and protein binding in serum of several antiepileptic drugs. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin Heidelberg New York, pp 262–273

    Google Scholar 

  • Johannessen SI, Strandjord RE ( 1975 b) The influence of phenobarbitone and phenytoin on carbamazepine serum levels. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin Heidelberg New York, pp 201–205

    Google Scholar 

  • Johannessen SI, Gerna M, Bakke J, Strandjord RE, Morselli PL (1976) CSF concentrations and serum protein binding of carbamazepine and carbamazepine 10,11-epoxide in epileptic patients. Br J Clin Pharmacol 3: 575–582

    CAS  Google Scholar 

  • Johannessen SI, Hendriksen O (1977) Serum levels of di-n-propylacetate in epileptic patients. Pharm Weekbl [Sci] 112: 287–289

    Google Scholar 

  • Jones TD, Jacobs JL (1932) The treatment of obstinate chorea with Nirvanol with notes on its mode of action. JAMA 99: 18–21

    Google Scholar 

  • Jordan BJ, Shillingford JS, Steed KP (1976) Preliminary observations on the protein-binding and enzyme-inducing properties of sodium valproate (Epilim). In: Legg, N (ed) Clinical and pharmacological aspects of sodium valproate (Epilim) in the treatment of epilepsy. MCS Consultants, Tunbridge Wells, pp 112–116

    Google Scholar 

  • Jusko WJ, Koup JR, Alvan G (1976) Nonlinear assessment of phenytoin bioavailability. J Pharmacokinet Biopharm 4: 327–336

    PubMed  CAS  Google Scholar 

  • Kallberg N, Agurell S, Ericsson O, Bucht E, Jailing B, Boreus LO (1975) Quantitation of phenobarbital and its main metabolites in human urine. Eur J Clin Pharmacol 9: 161–168

    PubMed  CAS  Google Scholar 

  • Kaneko S, Sato T, Suzuki K (1979) The levels of anticonvulsants in breast milk. Br J Clin Pharmacol 7: 624–627

    PubMed  CAS  Google Scholar 

  • Kangas L, Kanto J, Forsstrom J, Iisalo E (1976) Protein binding of diazepam and N-de-methyldiazepam in patients with poor renal function. Clin Nephrol 5: 114–118

    PubMed  CAS  Google Scholar 

  • Kanto J (1975) Plasma concentrations of diazepam and its metabolites after peroral, intramuscular, and rectal administration. Int J Clin Pharmacol Biopharm 12: 427–432

    PubMed  CAS  Google Scholar 

  • Kanto J, Iisalo E, Lehtinen V, Salminen J (1974) The concentration of diazepam and its metabolites in the plasma after an acute and chronic administration. Psychopharmacologia 36: 123–131

    PubMed  CAS  Google Scholar 

  • Kanto J, Kangas L, Surtola T (1975) Cerebrospinal fluid concentrations of diazepam and its metabolites in man. Acta Pharmacol Toxicol 36: 328–334

    CAS  Google Scholar 

  • Kaplan SA, Jack ML, Alexander K, Weinfeld RE (1973) Pharmacokinetic profile of diazepam in man following single intravenous and oral chronic oral administration. J Pharm Sci 62: 1789–1796

    PubMed  CAS  Google Scholar 

  • Kaplan SA, Alexander K, Jack ML, Puglisi CV, De Silva JAF, Lee TL, Weinfeld RE (1974) Pharmacokinetic profiles of clonazepam in dog and humans and of flunitrazepam in dog. J Pharm Sci 63: 527–537

    PubMed  CAS  Google Scholar 

  • Karlen B, Garle M, Rane A, Gutova M, Lindeborg B (1975) Assay of diphenylhydantoin (phenytoin) metabolites in urine by gas-chromatography. Metabolite pattern in humans. Eur J Clin Pharmacol 8: 359–363

    Google Scholar 

  • Kaufman RE, Habersang R, Lansky L (1977) Kinetics of primidone metabolism and excretion in children. Clin Pharmacol Ther 22: 200–205

    Google Scholar 

  • Kauko K, Tammisto P (1974) Comparison of two generically equivalent carbamazepine preparations. Ann Clin Res [Suppl II] 6: 21–25

    Google Scholar 

  • Kawashima K, Ishijima B, Yoshimizu N, Sato F (1980) Determination of dose-plasma concentration relationship of phenobarbital in epileptic patients by a new specific radioimmunoassay. Arch Int Pharmacodyn Ther 244: 166–176

    PubMed  CAS  Google Scholar 

  • Khoo K-C, Mendels J, Rothbart M, Garland WA, Colburn WA, Min BH, Lucek R, Carbone JJ, Boxenbaum HG, Kaplan SA (1980) Influence of phenytoin and phenobarbital on the disposition of single oral dose of clonazepam. Clin Pharmacol Ther 28: 368–375

    PubMed  CAS  Google Scholar 

  • Kinniburgh DW, Boyd ND (1981) Isolation of peptides from uremic plasma that inhibit phenytoin binding to normal plasma proteins. Clin Pharmacol Ther 30: 276–280

    PubMed  CAS  Google Scholar 

  • Klotz U, Antonin KH (1977) Pharmacokinetics and bioavailability of sodium valproate. Clin Pharmacol Ther 21: 736–743

    PubMed  CAS  Google Scholar 

  • Klotz U, Reimann I (1981) Clearance of diazepam can be impaired by its major metabolite desmethyldiazepam. Eur J Clin Pharmacol 21: 161–163

    PubMed  CAS  Google Scholar 

  • Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR (1975) The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55: 347–359

    PubMed  CAS  Google Scholar 

  • Klotz U, Antonin KH, Bieck PR (1976 a) Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat. J Pharmacol Exp Ther 199: 67–73

    Google Scholar 

  • Klotz U, Antonin KH, Bieck PR (1976 b) Comparison of the pharmacokinetics of diazepam after single and subchronic doses. Eur J Clin Pharmacol 10: 121–126

    Google Scholar 

  • Klotz U, Antonin KH, Briiger H, Bieck PR (1977) Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. Clin Pharmacol Ther 21: 430–436

    PubMed  CAS  Google Scholar 

  • Klotz U, Rapp T, Muller WA (1978) Disposition of valproic acid in patients with liver disease. Eur J Clin Pharmacol 13: 55–60

    PubMed  CAS  Google Scholar 

  • Knop HJ, Van Der Kleijn E, Edmunds LC (1975) Pharmacokinetics of clonazepam in man and laboratory animals. In: Schneider M, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin, pp 247–259

    Google Scholar 

  • Knudsen FO (1977) Plasma diazepam in infants after rectal administration in solution and by suppository. Acta Paediatr Scand 66: 563–567

    PubMed  CAS  Google Scholar 

  • Kostenbauer HB, Rapp RP, McGovern JP, Foster TS, Perrier DG, Blacker HM, Hulon WC, Kinkel AW (1975) Biovailability and single-dose pharmacokinetics of intramuscular phenytoin. Clin Pharmacol Ther 18: 449–456

    Google Scholar 

  • Koup JR, Rose JQ, Cohen ME (1978) Ethosuximide pharmacokinetics in a pregnant patient and her newborn. Epilepsia 19: 535–539

    PubMed  CAS  Google Scholar 

  • Kromann N, Christiansen J, Flachs H, Dam M, Hvidberg EF (1981) Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes. Ther Drug Monit 3: 239–246

    PubMed  CAS  Google Scholar 

  • Kumps AH (1981) Dose-dependency of the ratio between carbamazepine serum level and dosage in patients with epilepsy. Ther Drug Monit 3: 271–274

    PubMed  CAS  Google Scholar 

  • Küpfer A, Brilis GM, Watson JT, Harris TM (1980) A major pathway of mephenytoin metabolism in man. Aromatic hydroxylation to p-hydroxymephenytoin. Drug Metab Dispos 8: 1–4

    PubMed  Google Scholar 

  • Kupferberg HJ, Longacre-Shaw J (1979) Mephobarbital and phenobarbital plasma concentrations in epileptic patients treated with mephorbital. Ther Drug Monit 1: 117–122

    PubMed  CAS  Google Scholar 

  • Kupferberg HJ, Yonekawa W (1975) The metabolism of 3-methyl-5-ethyl-5-phenylhydantoin (mephenytoin) to 5-ethyl-5-phenylhydantoin ( Nirvanol) in mice in relation to anticonvulsant activity. Drug Metab Dispos 3: 26–29

    Google Scholar 

  • Kurata D, Wilkinson GR (1974) Erythrocyte uptake and plasma binding of diphenylhydantoin. Clin Pharmacol Ther 16: 677–684

    Google Scholar 

  • Kutt H, Winters W, Scherman R, McDowell F (1964) Diphenylhydantoin and phenobarbital toxicity. The role of liver disease. Arch Neurol 11: 649–656

    Google Scholar 

  • Kutt H, Wolk M, Scherman R, McDowell F (1964) Insufficient para-hydroxylation as a

    Google Scholar 

  • cause of diphenylhydantoin toxicity. Neurology 14:542–548

    Google Scholar 

  • Lai AA, Levy RH, Cutler RE (1978) Time course of interaction between carbamazepine and clonazepam in normal man. Clin Pharmacol Ther 24: 316–323

    PubMed  CAS  Google Scholar 

  • Lander CM, Eadie MJ, Tyrer JH (1977) Factors influencing plasma carbamazepine concentrations. Proc Aust Assoc Neurol 14: 184–193

    CAS  Google Scholar 

  • Lee HS, Chan KY (1981) Phenytoin and phenobarbitone plasma level-dose relationships in Chinese epileptic children in Singapore. Ther Drug Monit 3: 247–252

    PubMed  CAS  Google Scholar 

  • Leppik IE, Ramani V, Sawchuk R, Gumnit R (1979) Increased clearance of phenytoin during infectious mononucleosis. N Engl J Med 300: 481–482

    PubMed  CAS  Google Scholar 

  • Levy G (1976) Pharmacokinetic approaches to the study of drug interactions. Ann NY Acad Sci 281: 24–39

    PubMed  CAS  Google Scholar 

  • Levy RH (1980) Monitoring of free valproic acid levels? Ther Drug Monit 2: 199–201

    PubMed  CAS  Google Scholar 

  • Levy RH, Pitlick WH, Troupin AS, Green JR, Neal JM (1975) Pharmacokinetics of carbamazepine in normal man. Clin Pharmacol Ther 17: 657–668

    PubMed  CAS  Google Scholar 

  • Levy RH, Cenraud B, Loiseau P, Akbaraly R, Brachet-Liermain A, Guyot M, Gomeni R, Morselli PL (1980) Meal-dependent absorption of enteric-coated sodium valproate. Epilepsia 21: 273–280

    PubMed  CAS  Google Scholar 

  • Levy RH, Bowdle TA, Patel IH, Wilensky AJ (1981) Variability in valproate binding and clearance: implications in therapeutic monitoring. Epilepsia 22: 240–241

    Google Scholar 

  • Loiseau P, Brachet A, Henry P (1975) Concentration of dipropylacetate in plasma. Epilepsia 16: 609–61

    PubMed  CAS  Google Scholar 

  • Löscher W (1978) Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse. J Pharmacol Exp Ther 204: 255–261

    PubMed  Google Scholar 

  • Löscher W (1981) Concentration of metabolites of valproic acid in plasma of epileptic patients. Epilepsia 22: 169–178

    PubMed  Google Scholar 

  • Loughnan PM, Greenwald A, Purton WW, Aranda JV, Watters G, Neims AH (1977) Pharmacokinetic observations of phenytoin disposition in the newborn and young infant. Arch Dis Child 52: 302–309

    PubMed  CAS  Google Scholar 

  • Lous P (1954) Plasma levels and urinary excretion of three barbituric acids after oral administration to man. Acta Pharmacol Toxicol Ludden TM, Hawkins DW, Allen JP, Hoffman SF (1976) Optimum phenytoin-dosage regimens. Lancet 1: 307–308

    Google Scholar 

  • Ludden TM, Allen JP, Valutsky WA, Vicuna AV, Nappi JM, Hoffman SF, Wallace JE, Lalka D, McNay JL (1977) Individualization of phenytoin dosage regimens. Clin Pharmacol Ther 21: 287–293

    PubMed  CAS  Google Scholar 

  • Lund L (1974) Clinical significance of generic inequivalence of three different pharmaceutical preparations of phenytoin. Eur J Clin Pharmacol 7: 119–124

    PubMed  CAS  Google Scholar 

  • Lund L, Berlin A, Lunde PKM (1972) Plasma protein binding of diphenylhydantoin in patients with epilepsy. Clin Pharmacol Ther 13: 196–200

    PubMed  CAS  Google Scholar 

  • Lund L, Alvan G, Berlin A, Alexanderson B (1974) Pharmacokinetics of single and multiple doses of phenytoin in man. Eur J Clin Pharmacol 7: 81–86

    PubMed  CAS  Google Scholar 

  • Lund M, Sjö O, Hvidberg E (1973) Plasma concentrations of ethotoin in epileptic patients. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin Heidelberg New York, pp 111–114

    Google Scholar 

  • Lunde PKM, Rane A, Yaffe SJ, Lund L, Sjoqvist F (1970) Plasma protein binding of diphenylhydantoin in man. Interactions with other drugs and the effect of temperature and plasma dilution. Clin Pharmacol Ther 13: 196–200

    Google Scholar 

  • Lynn RK, Smith RG, Thompson RM, Deinzer ML, Griffin D, Gerber N (1978) Characterization of glucuronide metabolites of carbamazepine in human urine by gas-chroma-tography and mass-spectrometry. Drug Metab Dispos 6: 494–501

    PubMed  CAS  Google Scholar 

  • Mackichan J, Duffner PK, Cohen ME (1979) Adsorption of diazepam to plastic tubing. N Engl J Med 301: 332–333

    PubMed  CAS  Google Scholar 

  • Mackichan J, Duffner PK, Cohen ME (1981) Salivary concentrations and plasma protein binding of carbamazepine and carbamazepine 10,11-epoxide in epileptic patients. Br J Clin Pharmacol 12: 31–37

    PubMed  CAS  Google Scholar 

  • Makki KA, Perucca E, Richens A (1980) Metabolic effects of folic acid in folate-deficient epileptic patients. In: Johannessen SI et al. (eds) Antiepileptic therapy: advances in drug monitoring. Raven, New York, pp 391–398

    Google Scholar 

  • Mandelli M, Morselli PL, Nordio S, Pardi G, Sereni F, Tognoni G (1975) Placental transfer of diazepam and its disposition in the newborn infant. Clin Pharmacol Ther 17: 564–572

    PubMed  CAS  Google Scholar 

  • Mandelli M, Tognoni G, Garattini S (1978) Clinical pharmacokinetics of diazepam. Clin Pharmacokinet 3: 72–91

    PubMed  CAS  Google Scholar 

  • Martin E, Tozer TN, Sheiner LB, Riegelman S (1977) The clinical pharmacokinetics of phenytoin. J Pharmacokinet Biopharm 5: 579–596

    PubMed  CAS  Google Scholar 

  • Mattson RH, Cramer JA, Williamson PD, Novelly R (1978) Valproic acid in epilepsy: clinical and pharmacological effects. Ann Neurol 3: 20–25

    PubMed  CAS  Google Scholar 

  • Mawer GE, Mullen PW, Rodgers R, Robins AJ, Lucas SB (1974) Phenytoin dose adjustment in epileptic patients. Br J Clin Pharmacol 1: 163–168

    Google Scholar 

  • McAuliffe J J, Sherwin AL, Leppik IE, Fayle SA, Pippenger CE (1977) Salivary levels of anticonvulsants: a practical approach to drug monitoring. Neurology 27: 409–413

    PubMed  CAS  Google Scholar 

  • Meberg A, Langslet A, Bredesen JE, Lunde PKM (1978) Plasma concentration of diazepam and N-desmethyldiazepam in children after a single rectal or intramuscular dose of diazepam. Eur J Clin Pharmacol 14: 273–276

    PubMed  CAS  Google Scholar 

  • Meijer JWA, Hessing-Brandt L (1973) Determination of lower fatty acids, particularly the antiepileptic drug dipropylacetic acid, in biological material by means of microdiffusion and gas-chromatography. Clin Chim Acta 43: 215–222

    PubMed  CAS  Google Scholar 

  • Meijer JWA, Meinardi H (1976) Pharmacokinetic studies on sodium valproate. In: Legg NJ (ed) Clinical and pharmacological aspects of sodium valproate (Epilim) in the treatment of epilepsy. MCS Consultants, Tunbridge Wills pp 70–74

    Google Scholar 

  • Melander A (1978) Influence of food on the bioavailability of drugs. Clin Pharmacokinet 3: 337–351

    PubMed  CAS  Google Scholar 

  • Melander A, Brante G, Johansson O, Lindberg T, Wahlin-Boll E (1979) Influence of food on the absorption of phenytoin in man. Eur J Clin Pharmacol 15: 269–274

    PubMed  CAS  Google Scholar 

  • Melikian AP, Straughn AB, Slywka GWA, Whyatt PL, Meyer MC (1977) Bioavailability of 11 phenytoin products. J Pharmacokinet Biopharm 5: 133–146

    PubMed  CAS  Google Scholar 

  • Midha KK, Hindmarsh KW, McGilveray JJ, Cooper JK (1977) Identification of urinary catechol metabolites of phenytoin in humans, monkeys and dogs by GLC and GLC–mass spectrometry. J Pharm Sci 66: 1596–1602

    PubMed  CAS  Google Scholar 

  • Mihaly GW, Vajda FJ, Miles JL, Louis WJ (1979) Single and chronic dose pharmacokinetic studies of sodium valproate in epileptic patients. Eur J Clin Pharmacol 16: 23–29

    PubMed  CAS  Google Scholar 

  • Miller ME, Garland WA, Min BH, Ludwick BT, Ballard RH, Levy RH, (1981) Clonazepam acetylation in fast and slow acetylators. Clin Pharmacol Ther 30: 343–347

    PubMed  CAS  Google Scholar 

  • Mirkin BL (1971) Diphenylhydantoin: placental transport, fetal localization, neonatal metabolism, and possible teratogenic effects. J Pediatr 78: 329–337

    PubMed  CAS  Google Scholar 

  • Miyamoto K, Seino M, Ikeda Y (1975) Consecutive determination of the levels of twelve antiepileptic drugs in blood and cerebrospinal fluid. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin Heidelberg New York, pp 323–330

    Google Scholar 

  • Molenaar F, Korning B, Huizinga T (1979) Biopharmaceutics of rectal administration of drugs in man. 7. Absorption rate and bioavailability of phenobarbital and its sodium salt from rectal dosage forms. Int J Pharmaceutics 4: 99–110

    Google Scholar 

  • Molenaar F, Grunig WJ, Huizinga T (1980) Absorption rate and bioavailability of valproic acid and its sodium salt from rectal dosage form. Eur J Clin Pharmacol 17: 309–315

    Google Scholar 

  • Monaco F, Mutani R, Mastropaolo C, Tondi M (1979) Tears as the best practical indicator of the unbound fraction of an anticonvulsant drug. Epilepsia 20: 705–710

    PubMed  CAS  Google Scholar 

  • Monaco F, Piredda S, Mastropaolo G, Tondi M, Mutani R (1981) Diphenylhydantoin and primidone in tears. Epilepsia 22: 185–188

    PubMed  CAS  Google Scholar 

  • Monks A, Richens A (1979) Serum protein binding of valproic acid and its displacement by palmitic acid in vitro. Br J Clin Pharmacol 8: 187–189

    PubMed  CAS  Google Scholar 

  • Morris ME (1978) Compatibility of diazepam injection following dilution with intravenous fluids. Am J Hosp Pharm 35: 669–672

    PubMed  CAS  Google Scholar 

  • Morselli PL ( 1977 a) Psychotropic drugs. In: Morselli PL (ed) Drug disposition during development. Spectrum, New York, pp 431–476

    Google Scholar 

  • Morselli PL ( 1977 b) Antiepileptic drugs. In: Morselli PL (ed) Drug disposition during development. Spectrum, New York, pp 311–360

    Google Scholar 

  • Morselli PL, Franco-Morselli R (1980) Clinical pharmacokinetics of antiepileptic drugs in adults. Pharmacol Ther 10: 65–101

    PubMed  CAS  Google Scholar 

  • Morselli PL, Frigerio A (1975) Metabolism and pharmacokinetics of carbamazepine. Drug Metab Rev 4: 97–113

    PubMed  CAS  Google Scholar 

  • Morselli PL, Cassano GB, Placidi GF, Muscettola GB, Rizzo M ( 1973 a) Kinetics of the distribution of 14C-diazepam and its metabolites in various areas of cat brain. In: Garattini S, Mussini E, Randall O (eds) The benzodiazepines. Raven, New York, pp 129–143

    Google Scholar 

  • Morselli PL, Principi N, Tognoni G, Reali E, Belvedere G, Standen SM, Sereni F (1973 b) Diazepam elimination in premature and full-term infants and children. J Perinat Med 1: 133–141

    Google Scholar 

  • Morselli PL, Mandelli M, Tognoni G, Principi N, Pardi G, Sereni F (1974) Drug interaction in the human fetus and in the newborn infant. In: Morselli PL, Garattini S, Cohen SN (eds) Drug interactions. Raven, New York, pp 259–270

    Google Scholar 

  • Morselli PL, Monaco F, Gerna M, Recchia M, Riccio A (1975) Bioavailability of two carbamazepine preparations during chronic administration to epileptic patients. Epilepsia 16: 759–764

    PubMed  CAS  Google Scholar 

  • Morselli PL, Baruzzi A, Gerna M, Bossi L, Porta M (1977) Carbamazepine and carbamazepine-10,11-epoxide concentrations in human brain. Brit J Clin Pharmacol 4: 535–540

    CAS  Google Scholar 

  • Morselli PL, Franco-Morselli R, Bossi L (1980) Clinical pharmacokinetics in newborns and infants. Age-related differences and therapeutic implications. Clin Pharmacokinet 5: 485–527

    Google Scholar 

  • Mucklow JC, Bending MR, Kahn GC, Dollery CT (1978) Drug concentration in saliva. Clin Pharmacol Ther 24: 563–570

    PubMed  CAS  Google Scholar 

  • Mullen PW (1978) Optimal phenytoin therapy: a new technique for individualizing dosage. Clin Pharmacol Ther 23: 228–232

    PubMed  CAS  Google Scholar 

  • Mullen PW, Foster PW (1979) Comparative evaluation of six techniques for determining the Michaelis-Menten parameters relating phenytoin dose and steady-state serum concentrations. J Pharm Pharmacol 31: 100–104

    PubMed  CAS  Google Scholar 

  • Mygind KJ, Dam M, Christiansen J (1976) Phenytoin and phenobarbital plasma clearance during pregnancy. Acta Neurol Scand 54: 160–166

    PubMed  CAS  Google Scholar 

  • Naestoft J, Lund M, Larsen NE, Hvidberg E (1973) Assay and pharmacokinetics of clonazepam in humans. Acta Neurol, Scand 49: 103–108

    Google Scholar 

  • Nau H, Rating D, Hauser I, Jager E, Koch S, Helge H (1980) Placental transfer and pharmacokinetics of primidone and its metabolites phenobarbital, PEMA and hydroxyl-phenobarbital in neonates and infants of epileptic mothers. Eur J Clin Pharmacol 18: 31–41

    Google Scholar 

  • Neuvonen PJ (1979) Bioavailability of phenytoin: clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet 4: 91–103

    PubMed  CAS  Google Scholar 

  • Niebyl JR, Blake DA, Freeman JM, Luff RP (1979) Carbamazepine levels in pregnancy and lactation. Obstet Gyneaecol 53: 139–140

    CAS  Google Scholar 

  • Nishihara K, Uchino K, Saitoh Y, Honda Y, Makagawa F, Tamura Z (1979) Estimation of plasma unbound phenobarbital concentration by using mixed saliva. Epilepsia 20: 37–45

    PubMed  CAS  Google Scholar 

  • Nutt JG, Kupferberg HJ (1979) Linear relationship between plasma concentration and dosage of sodium valproate. Epilepsia 20: 589–592

    PubMed  CAS  Google Scholar 

  • Ochs H, Greenblatt DJ, Divoll M, Abernethy DR, Feyerabend H, Dengler HJ (1981) Diazepam kinetics in relation to age and sex. Pharmacology 23: 24–40

    PubMed  CAS  Google Scholar 

  • Odar-Cederlöf I (1977) Plasma protein binding of phenytoin and warfarin in patients undergoing renal transplantation. Clin Pharmacokinet 2: 147

    PubMed  Google Scholar 

  • Odar-Cederlöf I, Borgå O (1974) Kinetics of diphenylhydantoin in uraemic patients: consequences of decreased plasma protein binding. Eur J Clin Pharmacol 7: 31–37

    PubMed  Google Scholar 

  • Odar-Cederlöf I, Borgå O (1976) Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid. Clin Pharmacol Ther 20: 36–47

    PubMed  Google Scholar 

  • Oldigs HD, Bartels H, Wallis S, Warecka A, Grob-Selbeck G (1979) The effect of galenics on the blood level fluctuations of dipropylacetate -comparative investigation of small intestine-soluble coated pills and a retard form in children. Epilepsia 20: 85–90

    Google Scholar 

  • Olesen OV (1968) Determination of sulthiame (Ospolot®) in serum and urine by thin-layer chromatography: serum levels and urinary output in patients under long-term treatment. Acta Pharmacol Toxicol 26: 22–28

    CAS  Google Scholar 

  • Olsen GD, Bennett WM, Porter GA (1975) Morphine and phenytoin binding to plasma proteins in renal and hepatic disease. Clin Pharmacol Ther 17: 677–684

    PubMed  CAS  Google Scholar 

  • Painter MJ, Pippenger C, Carter G, Pitlick W (1977) Metabolism of phenobarbital and phenytoin by neonates with seizures. Neurology 27: 370

    Google Scholar 

  • Painter MJ, Pippenger C, Macdonald H, Pitlick W (1978) Phenobarbital and diphenylhydantoin levels in neonates with seizures. J Pediatr 92: 315–319

    PubMed  CAS  Google Scholar 

  • Palmer L, Bertilsson L, Collste P, Rawlins M (1973) Quantitative determination of carbamazepine in plasma by mass fragmentography. Clin Pharmacol Ther 14: 827–832

    PubMed  CAS  Google Scholar 

  • Patel IH, Levy RH (1979) Valproic acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsants and free fatty acids. Epilepsia 20: 85–90

    PubMed  CAS  Google Scholar 

  • Patel IH, Levy RH, Rapport RL (1977) Distribution characteristics of ethosuximide in discrete areas of rat brain. Epilepsia 18: 533–541

    PubMed  CAS  Google Scholar 

  • Patel IH, Levy RH, Venkataramanan R, Viswanathan CT, Moretti-Ojemann L (1980) Diurnal variation in protein binding of valproic acid and phenytoin and the role of free fatty acids. Clin Pharmacol Ther 22: 277

    Google Scholar 

  • Patrick MJ, Tilstone WJ, Reavey P (1972) Diazepam and breast feeding. Lancet 1: 542–543

    PubMed  CAS  Google Scholar 

  • Paxton JW, Foote S (1979) Aberrantly high phenytoin concentrations in saliva. Precaution in monitoring phenytoin concentration. Br J Clin Pharmacol 8: 508–509

    Google Scholar 

  • Paxton JW, Whiting B, Rowell F, Ratcliffe JG, Stephen KW (1976) Salivary concentrations of antiepileptic drugs. Lancet 2: 639–640

    Google Scholar 

  • Paxton JW, Rowell FJ, Ratcliffe JG, Lambie DG, Nanda R, Melville ID, Johnson RH (1977 a) Salivary phenytoin radioimmunoassay: a single method for the assessment of non protein bound drug concentrations. Eur J Clin Pharmacol 11: 71–74

    Google Scholar 

  • Paxton JW, Whiting B, Stephen KW (1977 b) Phenytoin concentrations in mixed parotid and submandibular saliva and serum measured by radioimmunoassay. Br J Clin Pharmacol 4: 185–192

    Google Scholar 

  • Perucca E (1980) Plasma protein binding of phenytoin in health and disease: relevance to therapeutic drug monitoring. Ther Drug Monit 2: 331–344

    PubMed  CAS  Google Scholar 

  • Perucca E, Richens A (1980) Reversal of carbamazepine-induced water intoxication by phenytoin: a pharmacokinetic interaction. J Neurol Neurosurg Psych 43: 540–545

    CAS  Google Scholar 

  • Perucca E, Makki K, Richens A (1978 a) Is phenytoin metabolism dose-dependent by enzyme-saturation or by feedback inhibition? Clin Pharmacol Ther 24: 46–51

    Google Scholar 

  • Perucca E, Garratt A, Hebdige S, Richens A (1978 b) Water intoxication in epileptic patients receiving carbamazepine. J Neurol Neurosurg Psych 41: 713–718

    Google Scholar 

  • Perucca E, Gatti G, Frigo GM, Crema A (1978 c) Pharmacokinetics of valproic acid after oral and intravenous administration. Br J Clin Pharmacol 5: 313–318

    Google Scholar 

  • Perucca E, Gatti G, Frigo GM, Crema A, Calzetti S, Visintini D (1978 d) Disposition of sodium valproate in epileptic patients. Br J Clin Pharmacol 5: 495–499

    Google Scholar 

  • Perucca E, Hebdige S, Gatti S, Lecchini S, Frigo GM, Crema A (1980 a) Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects. Clin Pharmacol Ther 28: 779–789

    Google Scholar 

  • Perucca E, Bittencourt P, Richens A (1980 b) Effect of dose increments on serum carbamazepine concentration in epileptic patients. Clin Pharmacokinet 6: 576–582

    Google Scholar 

  • Perucca E, Ruprah M, Richens A (1981 a) Altered drug binding to serum proteins in pregnant women: relevance to therapeutic drug monitoring. JR Soc Med 74: 422–426

    Google Scholar 

  • Perucca E, Ruprah M, Richens A, Park BK, Betteridge DJ, Hedges A (1981 b) Effect of low-dose phenobarbitone on five indirect indices of hepatic microsomal enzyme-induction and plasma lipoproteins in normal subjects. Br J Clin Pharmacol 12: 592–596

    Google Scholar 

  • Perucca E, Ruprah M, Richens A (1981 c) Decreased serum protein binding of diazepam and valproic acid in pregnant women. Br J Clin Pharmacol 12: 276 P

    Google Scholar 

  • Pinder RM, Brogden RN, Speight TM, Avery GS (1976) Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy. Drugs 12: 321–361

    PubMed  CAS  Google Scholar 

  • Pinder RM, Brogden RN, Speight TM, Avery GS (1977) Sodium valproate: a review of its pharmacological properties and therapeutic efficacy in epilepsy. Drugs 13: 81–123

    PubMed  CAS  Google Scholar 

  • Pippenger CE, Penry JK, Kutt H (1978) Antiepileptic drugs. Quantitative analysis and interpretation. Raven, New York, pp 326

    Google Scholar 

  • Pisani F, Fazio A, Oteri G, Di Perri R (1981) Dipropylacetic acid plasma levels; diurnal fluctuations during chronic treatment with dipropylacetamide. Ther Drug Monit 3: 297–301

    PubMed  CAS  Google Scholar 

  • Pitlick W, Painter M, Pippenger C (1978) Phenobarbital pharmacokinetics in neonates. Clin Pharmacol Ther 23: 346–350

    PubMed  CAS  Google Scholar 

  • Plasse JC, Revol M, Chabert G, Ducerf F (1979) Neonatal pharmacokinetics of valproic acid. In: Schaaf H, Van Der Kleijn E (eds) Progress in clinical pharmacy. Biomedical, Elsevier/North Holland, pp 247–252

    Google Scholar 

  • Porter RJ, Layzer RB ( 1975 Plasma albumin concentration and diphenylhydantoin binding in man. Arch Neurol 32: 298–303

    PubMed  CAS  Google Scholar 

  • Porter RJ, Penry JK, Lacy JR, Newmark ME, Kupferberg HJ (1979) Plasma concen–trations of phensuximide, methsuximide, and their metabolites in relation to clinical efficacy. Neurology 29: 1509–1513

    PubMed  CAS  Google Scholar 

  • Powell JR, Nelson E, Conrad KA, Likes K, Byers J, Perrier D (1983) Phenobarbital clearance, elimination with alkaline diuresis, and bioavailability in adults. Clin Pharmacol Ther 29: 273–274

    Google Scholar 

  • Pynnönen S (1977) The pharmacokinetics of carbamazepine in plasma and saliva of man. Acta Pharmacol Toxicol 41: 465–471

    Google Scholar 

  • Pynnonen S (1979) Pharmacokinetics of carbamazepine in man: a review. Ther Drug Monit 1: 409–431

    PubMed  CAS  Google Scholar 

  • Pynnönen S, Sillanpaa M (1975) Carbamazepine and mother’s milk. Lancet 11: 563

    Google Scholar 

  • Pynnönen S, Yrjana T (1977) The significance of the simultaneous determination of carbamazepine and its 10,11-epoxide from plasma and human erythrocytes. Int J Clin Pharmacol Biopharm 15: 222–226

    PubMed  Google Scholar 

  • Pynnönen S, Sillanpaa M, Frey H, Iisalo E (1977 a) Carbamazepine and its 10,11-epoxide in children and adults with epilepsy. Eur J Clin Pharmacol 11: 129–133

    Google Scholar 

  • Pynnönen S, Kanto J, Sillanpaa M, Erkkola R (1977 b) Carbamazepine: placental transport, tissue concentrations in foetus and newborn, and level in milk. Acta Pharmacol Toxicol 41: 244–253

    Google Scholar 

  • Pynnönen S, Sillanpaa M, Frey H, Iisalo E (1978) Carbamazepine and its 10,11-epoxide in children and adults with epilepsy. Eur J Clin Pharmacol 11: 129–133

    Google Scholar 

  • Pynnönen S, Frey H, Syllanpaa M (1980) The autoinduction of carbamazepine during

    Google Scholar 

  • Long-term therapy. Int J Clin Pharmacol Ther Toxicol 18:247–252

    Google Scholar 

  • Rambeck B (1979) Pharmacological interactions of mesuximide with phenobarbital and phenytoin in hospitalized epileptic patients. Epilepsia 20: 147–156

    PubMed  CAS  Google Scholar 

  • Rambeck B, Boenigk HE, Dunlop A, Mullen PW, Wadsworth J, Richens A (1979) Predicting phenytoin dose: a revised nomogram. Ther Drug Monit 2: 325–333

    Google Scholar 

  • Rane A, Tunell R (1981) Ethosuximide in human milk and in plasma of a mother and her nursed infant. Br J Clin Pharmacol 12: 855–858

    PubMed  CAS  Google Scholar 

  • Rane A, Lunde PKM, Jailing B, Yaffe SJ, Sjöqvist F (1971) Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinaemic infants. J Pediatr 78: 877–882

    PubMed  CAS  Google Scholar 

  • Rane A, Garle M, Borgå O, Sjöqvist F (1974) Plasma disappearance of transplacentally transferred diphenylhydantoin in the newborn studied by mass fragmentography. Clin Pharmacol Ther 13: 39–45

    Google Scholar 

  • Rane A, Bertilsson L, Palmer L (1975) Disposition of placentally transferred carbamazepine (Tegretol®) in the newborn. Eur J Clin Pharmacol 8: 283–284

    PubMed  CAS  Google Scholar 

  • Rane A, Hojer B, Wilson JT (1976) Kinetics of carbamazepine and its 10,11-epoxide metabolite in children. Clin Pharmacol Ther 19: 276–283

    PubMed  CAS  Google Scholar 

  • Rawlins MD, Collste P, Bertilsson L, Palmer L (1975) Distribution and elimination kinetics of carbamazepine in man. Eur J Clin Pharmacol 8: 91–96

    PubMed  CAS  Google Scholar 

  • Reidenberg MM, Odar-Cederlöf I, Von Bahr C, Borga O, Sjoqvist F (1971) Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. N Engl J Med 285: 264–267

    PubMed  CAS  Google Scholar 

  • Rey E, D’Athis P, De Lauture D, Dulac O, Aicardi J, Olive G (1979) Pharmacokinetics of carbamazepine in the neonate and the child. Int J Clin Pharmacol Biopharm 17: 90–96

    PubMed  CAS  Google Scholar 

  • Reynolds EH, Fenton G, Fenwick P, Johnson AL, Laundy M (1975) Interaction of phenytoin and primidone. Br Med J 2: 594–595

    PubMed  CAS  Google Scholar 

  • Reynolds F, Ziroyanis P, Jones N Smith SE (1976) Salivary phenytoin concentrations in epilepsy and in chronic renal failure. Lancet 11: 384–386

    Google Scholar 

  • Richens A (1975) A study of the pharmacokinetics of phenytoin (diphenylhydantoin) in epileptic patients and the development of a nomogram for making dose increments. Epilepsia 16: 627–646

    PubMed  CAS  Google Scholar 

  • Richens A (1979) Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet 4: 153–169

    PubMed  CAS  Google Scholar 

  • Richens A, Dunlop A (1975) Serum phenytoin levels in the management of epilepsy. Lancet 11: 247–248

    Google Scholar 

  • Richens A, Scoular IT, Ahmad S, Jordan BJ (1976) Pharmacokinetics and efficacy of Epilim in patients receiving long-term therapy with other antiepileptic drugs. In: Legg NJ (ed) Clinical and pharmacological aspects of sodium valproate (Epilim) in the treatment of epilepsy. MCS Consultants, Tunbridge Wells, pp 78–88

    Google Scholar 

  • Richter K, Terhaag B (1978) The relative bioavailability and pharmacokinetics of carba-mazepine. Int J Clin Pharmacol 16: 377–379

    CAS  Google Scholar 

  • Riva R, Albani F, Baruzzi A, Galvani I, Perucca E (1982) Determination of unbound valproic acid concentration in plasma by equilibrium dialysis and gas-liquid chromatography. Methodological aspects and observations in epileptic patients. Ther Drug Monit 4: 341–352

    Google Scholar 

  • Robinson JD, Morris BA, Aherne GW, Marks V (1975) Pharmacokinetics of a single dose of phenytoin in man measured by radioimmunoassay. Br J Clin Pharmacol 2: 345–350

    PubMed  CAS  Google Scholar 

  • Rossi LN, Nino LM, Principi N (1979) Correlation between age and plasma level/dosage ratio for phenobarbital in infants and children. Acta Paediatr Scand 68: 431–434

    PubMed  CAS  Google Scholar 

  • Routledge PA, Kitchell BB, Bjornsson TD, Skinner, BS, Linnoila M, Shand DG (1980 a) Diazepam and N-desmethyldiazepam redistribution after heparin. Clin Pharmacol Ther 27: 528–532

    Google Scholar 

  • Routledge PA, Stargel WW, Kitchell BB, Shand DG (1980 b) Determinants of plasma protein binding of diazepam. Clin Pharmacol Ther 27: 282

    Google Scholar 

  • Routledge PA, Stargel WW, Kitchell BB, Barchowsky A, Shand DG (1981) Sex related differences in the plasma protein binding of lignocaine and diazepam. Br J Clin Pharmacol 11: 245–250

    PubMed  CAS  Google Scholar 

  • Rylance GW, Butcher GM, Moreland T (1977) Saliva carbamazepine levels in children. Br Med J 2: 1481

    PubMed  CAS  Google Scholar 

  • Rylance GW, Moreland TA, Butcher GM (1979) Carbamazepine dose-frequency requirements in children. Arch Dis Child 54: 454–458

    PubMed  CAS  Google Scholar 

  • Sandor P, Sellers EM, Dumbrell RM, Khouw V (1981) Effect of short-and long-term alcohol use on phenytoin kinetics in chronic alcoholics. Clin Pharmacol Ther 30: 390–397

    PubMed  CAS  Google Scholar 

  • Sannita WG, Rapallino MV, Rodriguez G, Rosadini G (1980) EEG effects and plasma concentrations of phenobarbital in volunteers. Neuropharmacology 19: 927–930

    PubMed  CAS  Google Scholar 

  • Schmidt D, Kupferberg H (1975) Diphenylhydantoin, phenobarbital and primidone in saliva, plasma and CSF, Epilepsia 16: 735–741

    PubMed  CAS  Google Scholar 

  • Schobben F, Van Der Kleijn E, Gabreels FJM (1975) Pharmacokinetics of di-n-propylacetate in epileptic patients. Eur J Clin Pharmacol 8: 97–105

    PubMed  CAS  Google Scholar 

  • Schottelius DD, Fincham RW (1978) Clinical application of serum primidone levels. In: Pippenger CE, Penry JK, Kutt H (eds) Antiepileptic drugs, quantitative analysis and interpretation. Raven, New York, pp 273–282

    Google Scholar 

  • Sherwin AL (1978) Clinical pharmacology of ethosuximide. In: Pippenger CE, Penry JK, Kutt H (eds) Antiepileptic drugs: quantitative analysis and interpretation. Raven, New York, pp 283–295

    Google Scholar 

  • Sherwin AL, Robb JP (1972) Ethosuximide: relation of plasma level to clinical control. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 443–448

    Google Scholar 

  • Sherwin AL, Eisen AA, Sokolowsky CD (1973) Anticonvulsant drugs in human epileptogenic brain. Correlation of phenobarbital and diphenylhydantoin levels with plasma. Arch Neurol 29: 73–77

    Google Scholar 

  • Sironi VA, Cabrini G, Porro MG, Ravagnati L, Marossero F (1980) Antiepileptic drug distribution in cerebral cortex, Ammons’s horn, and amygdala of man. J Neurosurg 52: 686–692

    Google Scholar 

  • Sjö O, Hvidberg EF, Naestoft J, Lund M (1975 a) Pharmacokinetics and side effects of clonazepam and its 7-amino metabolite in man. Eur J Clin Pharmacol 8: 249–254

    Google Scholar 

  • Sjö O, Hvidberg EF, Larsen N-E, Lund M, Naestoft J (1975 b) Dose-dependent kinetics of ethotoin in man. Exp Pharmacol Physiol 2: 185–192

    Google Scholar 

  • Sjoholm I, Kober A, Odar–Cederlof I, Borga O (1976) Protein binding of drugs in uremic and normal serum. The role of endogenous binding inhibitors. Biochem Pharmacol 25: 1205–1213

    Google Scholar 

  • Sloan TP, Idle JR, Smith RL (1981) Influence of DH/DL alleles regulating debrisoquine oxidation on phenytoin metabolism. Clin Pharmacol Ther 29: 493–497

    PubMed  CAS  Google Scholar 

  • Smith RG, Davies GD, Lynn RK, Gerber N (1977) Hydantoin ring glucuronidation: characterization of a new metabolite of 5,5–diphenylhydantoin in man and the rat. Biomed Mass Spectrom 4: 275–279

    PubMed  CAS  Google Scholar 

  • Smith GA, McKauge L, Dubetz D, Tyrer JH, Eadie MJ (1979) Factors influencing plasma concentrations of ethosuximide. Clin Pharmacokinet 4: 38–52

    PubMed  CAS  Google Scholar 

  • Stewart MJ, Ballinger BR, Devlin EJ, Miller AY, Ramsay AC (1975) Bioavailability of phenytoin. A comparison of two preparations. Eur J Clin Pharmacol 9: 209–212

    Google Scholar 

  • Strandjord RE, Johannessen SI (1974) One daily dose of diphenylhydantoin for patients with epilepsy. Epilepsia 15: 317–327

    PubMed  CAS  Google Scholar 

  • Strandjord RE, Johannessen SI (1975) A preliminary study of serum carbamazepine levels in healthy subjects and in patients with epilepsy. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin A (eds) Clinical pharmacology of antiepileptic drugs. Springer, Berlin Heidelberg New York, pp 181–188

    Google Scholar 

  • Strandjord RE, Johannessen SI (1980) Single drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect. Epilepsia 21: 655–662

    PubMed  CAS  Google Scholar 

  • Strong JM, Abe T, Gibbs EL, Atkinson AJ Jr (1974) Plasma levels of methsuximide and N-desmethyl-methsuximide during methsuximide therapy. Neurology 24: 250–255

    PubMed  CAS  Google Scholar 

  • Svendsen A, Brochmann-Hanssen E (1962) Gas chromatography of barbiturates: application to the study of their metabolism and excretion in humans. J Pharm Sci 51: 494–495

    PubMed  CAS  Google Scholar 

  • Svensmark O, Buchthal F (1963) Accumulation of phenobarbital in man. Epilepsia 4: 199–206

    PubMed  CAS  Google Scholar 

  • Svensmark O, Buchthal F (1964) Diphenylhydantoin and phenobarbital. Serum levels in children. Am J Dis Child 108: 82–87

    Google Scholar 

  • Tammisto P, Kauko K, Viukari M (1976) Bioavailability of phenytoin. Lancet 1: 254–255

    PubMed  CAS  Google Scholar 

  • Tang BK, Kalow W, Grey AA (1979) Metabolic fate of phenobarbital in man. N-Glucoside formation. Drug Metab Dispos 7: 315–318

    PubMed  CAS  Google Scholar 

  • Tedeschi G, Cenraud B, Guyot M, Gomeni R, Morselli PL, Levy RH, Loiseau P (1981) Influence of food on carbamazepine absorption. In: Dam M, Gram L, Penry JK (eds) Advances in epileptology: XIIth epilepsy international symposium. Raven, New York, pp 563–567

    Google Scholar 

  • Terhaag B, Richter K, Diettrich H (1978) Concentration behaviour of carbamazepine in bile and plasma of man. Int J Clin Pharmacol 16: 607–609

    CAS  Google Scholar 

  • Thiessen J J, Sellers EM, Denbeigh P, Dolman L (1976) Plasma protein binding of diazepam and tolbutamide in chronic alcoholics. J Clin Pharmacol 16: 345–351

    PubMed  CAS  Google Scholar 

  • Thompson RM, Beghin J, Fife WK, Gerber N (1976) 5,5-bis (4-hydroxyphenyl)hydantoin, a minor metabolite of diphenylhydantoin ( Dilantin) in the rat and human. Drug Metab Dispos 4: 349–356

    Google Scholar 

  • Tognoni G, Gomeni R, De Maio D, Alberti GG, Franciosi P, Sireghi G (1975) Pharmacokinetics of N-demethyldiazepam in patients suffering from insomnia and treated with nortriptyline. Br J Clin Pharmacol 2: 227–232

    PubMed  CAS  Google Scholar 

  • Tomson T, Tybring G, Bertilsson L, Ekbom C, Rane A (1980) Carbamazepine therapy in trigeminal neuralgia. Clinical effects in relation to plasma concentration. Arch Neurol 37: 699–703

    Google Scholar 

  • Triedman HM, Fishman RA, Yahr MD (1960) Determination of plasma and cerebrospinal fluid levels of Dilantin in the human. Trans Am Neurol Assoc 85: 166–169

    PubMed  CAS  Google Scholar 

  • Troupin AS, Friel (1975) Anticonvulsant levels in saliva, serum and cerebrospinal fluid. Epilepsia 16: 223–227

    CAS  Google Scholar 

  • Troupin AS, Moretti-Ojemann L, Dodrill CB (1976) Mephenytoin: a reappraisal. Epilepsia 17: 403–414

    PubMed  CAS  Google Scholar 

  • Troupin AS, Green JR, Levy RH (1974) Carbamazepine as an anticonvulsant: a pilot study. Neurology 24: 863–869

    PubMed  CAS  Google Scholar 

  • Tyrer JH, Eadie MJ, Sutherland JM, Hooper WD (1974) Outbreak of anticonvulsant in-toxication of an Australian city. Br Med J 4: 271–273

    Google Scholar 

  • Vajda F, Williams FM, Davidson S, Falconer MA, Breckenridge A (1974) Human brain, cerebrospinal fluid and plasma concentrations of diphenylhydantoin and phenobarbital. Clin Pharmacol Ther 15: 597–603

    PubMed  CAS  Google Scholar 

  • Van Der Velde, EA, Driessen O (1981) Prediction of phenytoin dosage in relation to the variability of phenytoin plasma concentration. Br J Clin Pharmacol 1: 41–52

    Google Scholar 

  • Vasko MR, Bell RD, Daly DD, Pippenger CEJ (1980) Inheritance of phenytoin hypometabolism: a kinetic study of one family. Clin Pharmacol Ther 27: 96–103

    PubMed  CAS  Google Scholar 

  • Viswanathan CT, Booker HE, Welling PG (1978) Bioavailability of oral and intramuscular phenobarbital. J Clin Pharmacol 18: 100–105

    PubMed  CAS  Google Scholar 

  • Viswanathan CT, Booker HE, Welling PG (1979) Pharmacokinetics of phenobarbital following single and repeated doses. J Clin Pharmacol 19: 282–289

    PubMed  CAS  Google Scholar 

  • Waddell WJ, Butler TC (1957 a) The distribution and excretion of phenobarbital. J Clin Invest 36: 1217–1226

    Google Scholar 

  • Waddell WJ, Butler TC (1957 b) Renal excretion of 5,5-dimethyl-2,4-oxazolidinedione (product of demethylation of trimethiadione). Proc Soc Exp Biol Med 96: 563–565

    Google Scholar 

  • Wallace S, Brodie MJ (1976) Decreased drug binding in serum from patients with chronic hepatic disease. Eur J Clin Pharmacol 9: 429–432

    CAS  Google Scholar 

  • Wallin A, Jailing B, Boreus LO (1974) Plasma concentrations of phenobarbital in the neonate during prophylaxis for neonatal hyperbilirubinemia. J Pediatr 85: 392–397

    PubMed  CAS  Google Scholar 

  • Walson PD, Mimaki T, Curless R, Mayersohn M, Perrier D (1980) Once daily doses of phenobarbital in children. J Pediatr 97: 303–305

    PubMed  CAS  Google Scholar 

  • Warren JW, Benmaman JD, Braxton B, Wannamaker BB, Levy RH (1980) Kinetics of a carbamazepine-ethosuximide interaction. Clin Pharmacol Ther 28: 646–651

    PubMed  CAS  Google Scholar 

  • Westenberg HGM, Van Der Kleijn E, Oei TT, De Zeeuw RA (1978) Kinetics of carbamazepine and carbamazepine-epoxide, determined by use of plasma and saliva. Clin Pharmacol Ther 23: 320–328

    PubMed  CAS  Google Scholar 

  • Whyte MP, Dekaban AS (1977) Metabolic fate of phenobarbital. A quantitative study of p-hydroxyphenobarbital elimination in man. Drug Metab Dispos 5: 63–70

    PubMed  CAS  Google Scholar 

  • Wilder BJ, Ramsay RE (1976) Oral and intramuscular phenytoin. Clin Pharmacol Ther 19: 360–364

    PubMed  CAS  Google Scholar 

  • Wilder BJ, Serrano EE, Ramsay E (1973) Plasma diphenylhydantoin levels after loading and maintenance doses. Clin Pharmacol Ther 14: 797–801

    PubMed  CAS  Google Scholar 

  • Wilder BJ, Serrano EE, Ramsey E, Buchanan RA (1974) A method for shifting from oral to intramuscular diphenylhydantoin administration. Clin Pharmacol Ther 16: 507–513

    PubMed  CAS  Google Scholar 

  • Wilder BJ, Ramsay RE, Willmore LJ, Feussner GF, Perchalski RJ, Shumate JB (1977) Efficacy of intravenous phenytoin in the treatment of status epilepticus: kinetics of central nervous system penetration. Ann Neurol 1: 511–518

    PubMed  CAS  Google Scholar 

  • Wilensky AJ, Levy RH, Troupin AS, Moretti-Ojemann L, Friel P (1978) Clorazepat kinetics in treated epileptics. Clin Pharmacol Ther 24: 22–30

    PubMed  CAS  Google Scholar 

  • Wilensky AJ, Lowden J A (1973) Inadequate serum levels after intramuscular administration of diphenylhydantoin. Neurology 23: 318–324

    PubMed  CAS  Google Scholar 

  • Wilson JT, Wilkinson GR (1973) Chronic and severe phenobarbital intoxication in a child treated with primidone and diphenylhydantoin. J Pediatr 83: 484–489

    PubMed  CAS  Google Scholar 

  • Wilson JT, Hojer B, Rane A (1976) Loading and conventional dose therapy with phenytoin in children; kinetic profile of parent drug and main metabolite in plasma. Clin Pharmacol Ther 20: 48–58

    PubMed  CAS  Google Scholar 

  • Wilson JT, Brown RD, Cherek DR, Dail JW, Hilman B, Jobe PC, Manno BR, Manno JE, Redetzki HM, Stewart J J (1980) Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences. Clin Pharmacokinet 5: 1–66

    PubMed  CAS  Google Scholar 

  • Withrow CD, Woodbury DM (1972) Trimethadione and other oxazolidinediones. Absorption, distribution and excretion. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 389–392

    Google Scholar 

  • Woodbury DM (1972) Sulfonamides and derivatives Acetazolamide. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic drugs. Raven, New York, pp 465–475

    Google Scholar 

  • Wulff K, Flachs H, Wurtz-Jorgensen A, Gram L (1977) Clinical pharmacological aspects of valproate sodium. Epilepsia 18: 149–157

    PubMed  CAS  Google Scholar 

  • Yacobi A, Lampmann T, Levy G (1977) Frequency of distribution of free warfarin and free phenytoin fraction values in serum of healthy human adults. Clin Pharmacol Ther 21: 283–286

    PubMed  CAS  Google Scholar 

  • Zimmermann CL, Patel IH, Levy RH, Edwards D, Nelson SD, Hutchinson M (1981) Protein binding of valproic acid in the presence of elevated free fatty acids in patient and normal human serum. Epilepsia 22: 11–17

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Perucca, E., Richens, A. (1985). Clinical Pharmacokinetics of Antiepileptic Drugs. In: Frey, HH., Janz, D. (eds) Antiepileptic Drugs. Handbook of Experimental Pharmacology, vol 74. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69518-6_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69518-6_24

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-69520-9

  • Online ISBN: 978-3-642-69518-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics