Clinical Pharmacokinetics

, Volume 46, Issue 11, pp 897–939 | Cite as

Pharmacokinetic Considerations in Clinical Toxicology

Clinical Applications
Review Article


Pharmacokinetic and pharmacodynamic principles should be regarded in the assessment and proper management of patients exposed to a poison. Clinicians must apply these principles to make rational clinical decisions regarding the significance of the poisoning (risk assessment) and to formulate an appropriate management plan. However, pharmacokinetic processes and parameters may be changed in the patient with acute poisoning. This may result from saturation of the capacity of a number of physiological processes due to the high dose, or the toxic effects of the poison may change these processes directly. For example, absorption kinetics may be altered because of increased gastrointestinal transit time (e.g. cholinergic receptor antagonists) or saturable absorption (e.g. methotrexate). Saturation of protein binding may increase the volume of distribution and thereby increase the elimination half-life (e.g. salicylates). Alteration of the acid-base balance (poison-induced or iatrogenic) may also increase or decrease the distribution of a poison. Saturation of metabolism at high doses can prolong toxicity (e.g. phenytoin) or lead to other routes of metabolism that lead to increased toxicity (e.g. paracetamol [acetaminophen]). Excretion may be reduced by saturation of active transporters or decreased renal blood flow.

A better understanding of pharmacokinetic principles should improve the clinical care of patients. It should lead to more accurate interpretation of blood concentrations or biomarkers (e.g. ECG intervals or acetylcholinesterase activity) and how these relate to the time course for that poison, and better prediction of prognosis. This in turn, indicates the appropriate duration of observation and the requirement for some specific treatments. Many specific poisoning treatments aim to favourably alter the pharmacokinetics of the poison. These include activated charcoal, whole bowel irrigation, extracorporeal elimination, chelating agents, antitoxins and urinary alkalinisation. The evidence supporting them, their indications and limitations can only be understood using pharmacokinetic principles. These principles also underpin the appropriate choice within the flexible dosage regimen for many antidotes. In particular, naloxone, flumazenil, methylene blue, atropine and pralidoxime all use variable doses and have an elimination half-life that is much shorter than many (but not all) of the poisons treated by these agents. A firm grounding in pharmacokinetics/toxicokinetics should be regarded as a core competency for all professionals involved in clinical care or undertaking research in clinical toxicology.


Central Compartment Peripheral Compartment Molecular Adsorbent Recirculate System Propanil Distribution Kinetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Darren Roberts drafted the manuscript in discussion with Nick Buckley and it was subsequently improved by both authors. Dr Roberts acknowledges the support of the National Health and Medical Research Council (Australia). The South Asian Clinical Toxicology Research Collaboration is funded by Wellcome Trust/National Health and Medical Research Council International Collaborative Research Grant GR071669MA.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Baud FJ. Pharmacokinetic-pharmacodynamic relationships. How are they useful in human toxicology? Toxicol Lett 1998; 102–103: 643–8PubMedGoogle Scholar
  2. 2.
    Daly FFS, Little M, Murray L. A risk assessment based approach to the management of acute poisoning. Emerg Med J 2006; 23: 396–9PubMedGoogle Scholar
  3. 3.
    van Rossum JM, van Lingen G, Burgers JP. Dose-dependent pharmacokinetics. Pharmacol Ther 1983; 21(1): 77–99PubMedGoogle Scholar
  4. 4.
    Rosenberg J, Benowitz NL, Pond S. Pharmacokinetics of drug overdose. Clin Pharmacokinet 1981; 6(3): 161–92PubMedGoogle Scholar
  5. 5.
    Slikker Jr W, Andersen ME, Bogdanffy MS, et al. Dose-dependent transitions in mechanisms of toxicity. Toxicol Appl Pharmacol 2004; 201(3): 203–25PubMedGoogle Scholar
  6. 6.
    DuBuske LM. The role of P-glycoprotein and organic anion-transporting polypeptides in drug interactions. Drug Saf 2005; 28(9): 789–801PubMedGoogle Scholar
  7. 7.
    Ludden TM. Nonlinear pharmacokinetics: clinical implications. Clin Pharmacokinet 1991; 20(6): 429–46PubMedGoogle Scholar
  8. 8.
    Pond SM, Tozer TN. First-pass elimination: basic concepts and clinical consequences. Clin Pharmacokinet 1984; 9(1): 1–25PubMedGoogle Scholar
  9. 9.
    Sue YJ, Shannon M. Pharmacokinetics of drugs in overdose. Clin Pharmacokinet 1992; 23(2): 93–105PubMedGoogle Scholar
  10. 10.
    Chyka PA. Challenges of toxicokinetic studies for cases of human poisoning [abstract]. In: XXI International Congress of the European Association of Poisons Centres and Clinical Toxicologists; 2001 May 16–19; Barcelona. J Toxicol Clin Toxicol 2001; 39(3): 209–10Google Scholar
  11. 11.
    McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004; 56(2): 163–84PubMedGoogle Scholar
  12. 12.
    Yu LX, Crison JR, Amidon JL. Compartmental transit and dispersion model analysis of small intestinal transit flow in humans. Int J Pharm 1996; 140(1): 111–8Google Scholar
  13. 13.
    Roberts DM, Southcott E, Potter JM, et al. Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal. Ther Drug Monit 2006; 28(6): 784–92PubMedGoogle Scholar
  14. 14.
    Eyer F, Meischner V, Kiderlen D, et al. Human parathion poisoning: a toxicokinetic analysis. Toxicol Rev 2003; 22(3): 143–63PubMedGoogle Scholar
  15. 15.
    Bennett PN, Davies DS, Hawksworth GM. In vivo absorption studies with paraquat and diquat in the dog [abstract]. Br J Pharmacol 1976; 58: 284PPubMedGoogle Scholar
  16. 16.
    Green R, Sitar DS, Tenenbein M. Effect of anticholinergic drugs on the efficacy of activated charcoal. J Toxicol Clin Toxicol 2004; 42(3): 267–72PubMedGoogle Scholar
  17. 17.
    Rashid MU, Bateman DN. Effect of atropine on gastric emptying, paracetamol absorption, salivary flow and heart rate in young and fit elderly volunteers. Br J Clin Pharmacol 1990; 30: 25–34PubMedGoogle Scholar
  18. 18.
    Consolo S, Morselli PL, Zaccala M, et al. Delayed absorption of phenylbutazone caused by desmethyl imipramine in humans. Eur J Clin Pharmacol 1970; 10(2): 239–42Google Scholar
  19. 19.
    Nimmo J, Heading RC, Tothill P, et al. Pharmacological modification of gastric emptying: effects of propantheline and metoclopramide on paracetamol absorption. BMJ 1973; 1(5853): 587–9PubMedGoogle Scholar
  20. 20.
    Morgan JP, Nathan G, Rivera-Calimlim L, et al. Imipramine caused interference with levodopa absorption from the gastrointestinal tract in rats. J Pharmacol Exp Ther 1975; 192(2): 451–7PubMedGoogle Scholar
  21. 21.
    Halcomb SE, Sivilotti MLA, Goklaney A, et al. Pharmacokinetic effects of diphenhydramine or oxycodone in simulated acetaminophen overdose. Acad Emerg Med 2005; 12(2): 169–72PubMedGoogle Scholar
  22. 22.
    Roberts MS, Magnusson BM, Burczynski FJ, et al. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet 2002; 41(10): 751–90PubMedGoogle Scholar
  23. 23.
    Rivera-Calimlim L. Problems of therapeutic drug monitoring of chlorpromazine. Ther Drug Monit 1982; 4: 41–9PubMedGoogle Scholar
  24. 24.
    Buckley NA, Dawson AH, Reith DA. Controlled release drugs in overdose: clinical considerations. Drug Saf 1995; 12(1): 73–84PubMedGoogle Scholar
  25. 25.
    Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1–3): 3–26PubMedGoogle Scholar
  26. 26.
    Jung D, Powell JR, Walson P, et al. Effect of dose on phenytoin absorption. Clin Pharmacol Ther 1980; 28(4): 479–85PubMedGoogle Scholar
  27. 27.
    Eyer F, Felgenhauer N, Gempel K, et al. Acute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy. J Clin Psychopharmacol 2005; 25(4): 376–80PubMedGoogle Scholar
  28. 28.
    Isbister GK, Hackett LP, Dawson AH, et al. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Br J Clin Pharmacol 2003; 56(4): 441–50PubMedGoogle Scholar
  29. 29.
    Roberts DM, Seneviratne R, Mohammed F, et al. Intentional self-poisoning with the chlorophenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA). Ann Emerg Med 2005; 46(3): 275–84PubMedGoogle Scholar
  30. 30.
    Tenenbein M. Toxicokinetics and toxicodynamics of iron poisoning. Toxicol Lett 1998; 103: 653–6Google Scholar
  31. 31.
    Needs CJ, Brooks PM. Clinical pharmacokinetics of the salicylates. Clin Pharmacokinet 1985; 10(2): 164–77PubMedGoogle Scholar
  32. 32.
    Chyka PA, Seger D, Krenzelok EP, et al. American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2): 61–87Google Scholar
  33. 33.
    Neuvonen PJ. Clinical pharmacokinetics of oral activated charcoal in acute intoxications. Clin Pharmacokinet 1982; 7(6): 465–89PubMedGoogle Scholar
  34. 34.
    Eyer P, Sprenger M. Oral administration of activated charcoal-sorbitol suspension as first aid in prevention of poison resorption? [in German]. Klin Wochenschr 1991; 69(19): 887–94PubMedGoogle Scholar
  35. 35.
    Stewart BH, Kugler AR, Thompson PR, et al. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res 1993; 10(2): 276–81PubMedGoogle Scholar
  36. 36.
    McLean MJ. Clinical pharmacokinetics of gabapentin. Neurology 1994; 44 (6 Suppl. 5): S17–22PubMedGoogle Scholar
  37. 37.
    Thurnham DI, Northrop-Clewes CA. Optimal nutrition: vitamin A and the carotenoids. Proc Nutr Soc 1999; 58(2): 449–57PubMedGoogle Scholar
  38. 38.
    Blanchard J, Tozer TN, Rowland M. Pharmacokinetic perspectives on megadoses of ascorbic acid. Am J Clin Nutr 1997; 66(5): 1165–71PubMedGoogle Scholar
  39. 39.
    Beer TM, Munar M, Henner WD. A phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation. Cancer 2001; 91(12): 2431–9PubMedGoogle Scholar
  40. 40.
    Hoekstra M, Haagsma C, Neef C, et al. Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in patients with rheumatoid arthritis. J Rheumatol 2006; 33(3): 481–5PubMedGoogle Scholar
  41. 41.
    Balis FM, Savitch JL, Bleyer WA. Pharmacokinetics of oral methotrexate in children. Cancer Res 1983; 43(5): 2342–5PubMedGoogle Scholar
  42. 42.
    Henderson ES, Adamson RH, Oliverio VT. The metabolic fate of tritiated methotrexate: II. Absorption and excretion in man. Cancer Res 1965; 25(7): 1018–24PubMedGoogle Scholar
  43. 43.
    Jaeger A, Sauder P, Kopferschmitt J, et al. When should dialysis performed in lithium poisoning? A kinetic study in 14 cases of lithium poisoning. J Toxicol Clin Toxicol 1993; 31(3): 429–47PubMedGoogle Scholar
  44. 44.
    Roberts MS. Targeted drug delivery to the skin and deeper tissues: role of physiology, solute structure and disease. Clin Exp Pharmacol Physiol 1997; 24(11): 874–9PubMedGoogle Scholar
  45. 45.
    Nolan RJ, Rick DL, Freshour NL, et al. Chlorpyrifos: pharmacokinetics in human volunteers. Toxicol Appl Pharmacol 1984; 73: 8–15PubMedGoogle Scholar
  46. 46.
    Okumura T, Takasu N, Ishimatsu S, et al. Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med 1996; 28(2): 129–35PubMedGoogle Scholar
  47. 47.
    Little M, Murray L. Consensus statement: risk of nosocomial organophosphate poisoning in emergency departments. Emerg Med Australas 2004; 16(5–6): 456–8PubMedGoogle Scholar
  48. 48.
    Roberts D, Senarathna L. Secondary contamination in organophosphate poisoning. QJM 2004; 97(10): 697–8PubMedGoogle Scholar
  49. 49.
    Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002; 40(1): 3–20PubMedGoogle Scholar
  50. 50.
    Buckley NA, Whyte IM, O’Connell DL, et al. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol 1999; 37(6): 753–7PubMedGoogle Scholar
  51. 51.
    Greenblatt DJ. Elimination half-life of drugs: value and limitations. Annu Rev Med 1985; 36: 421–7PubMedGoogle Scholar
  52. 52.
    Atkinson Jr AJ, Ruo TI, Frederiksen MC. Physiological basis of multicompartmental models of drug distribution. Trends Pharmacol Sci 1991; 12(3): 96–101PubMedGoogle Scholar
  53. 53.
    Lombardo F, Obach RS, Shalaeva MY, et al. Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data. J Med Chem 2002; 45(13): 2867–76PubMedGoogle Scholar
  54. 54.
    Oakley PW, Whyte IM, Carter GL. Lithium toxicity: an iatrogenic problem in susceptible individuals. Aust N Z J Psychiatry 2001; 35(6): 833–40PubMedGoogle Scholar
  55. 55.
    Frazer A, Mendels J, Secunda SK, et al. The prediction of brain lithium concentrations from plasma or erythrocyte measures. J Psychiatr Res 1973; 10(1): 1–7PubMedGoogle Scholar
  56. 56.
    Thanacoody HKR, Thomas SHL. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev 2005; 24(3): 205–14PubMedGoogle Scholar
  57. 57.
    Henry JA, Cassidy SL. Membrane stabilising activity: a major cause of fatal poisoning. Lancet 1986; I(8495): 1414–7Google Scholar
  58. 58.
    Albertson TE, Dawson A, de Latorre F, et al. TOX-ACLS: toxicologic-oriented advanced cardiac life support [abstract]. In: Proceedings of the International Guidelines 2000 Conference for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Ann Emerg Med 2001; 37 (4 Suppl.): S78–90PubMedGoogle Scholar
  59. 59.
    Bradberry SM, Thanacoody HKR, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev 2005; 24(3): 195–204PubMedGoogle Scholar
  60. 60.
    Brown TC, Barker GA, Dunlop ME, et al. The use of sodium bicarbonate in the treatment of tricyclic antidepressant-induced arrhythmias. Anaesth Intensive Care 1973; 1(3): 203–10PubMedGoogle Scholar
  61. 61.
    Levitt MA, Sullivan Jr JB, Owens SM, et al. Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose. Am J Emerg Med 1986; 4(2): 121–5PubMedGoogle Scholar
  62. 62.
    Pentel PR, Keyler DE. Effects of high dose alpha-1-acid glycoprotein on desipramine toxicity in rats. J Pharmacol Exp Ther 1988; 246(3): 1061–6PubMedGoogle Scholar
  63. 63.
    Hinderling PH, Hartmann D. The pH dependency of the binding of drugs to plasma proteins in man. Ther Drug Monit 2005; 27(1): 71–85PubMedGoogle Scholar
  64. 64.
    Franssen EJF, Kunst PWA, Bet PM, et al. Toxicokinetics of nortriptyline and amitriptyline: two case reports. Ther Drug Monit 2003; 25(2): 248–51PubMedGoogle Scholar
  65. 65.
    Hulten BA, Heath A, Knudsen K, et al. Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics. J Toxicol Clin Toxicol 1992; 30(2): 171–9PubMedGoogle Scholar
  66. 66.
    Goldberg MA, Barlow CF, Roth LJ. The effects of carbon dioxide on the entry and accumulation of drugs in the central nervous system. J Pharmacol Exp Ther 1961; 131: 308–18PubMedGoogle Scholar
  67. 67.
    Hill JB. Experimental salicylate poisoning: observations on the effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics 1971; 47(4): 658–65PubMedGoogle Scholar
  68. 68.
    Buchanan N, Kundig H, Eyberg C. Experimental salicylate intoxication in young baboons: a preliminary report. J Pediatr 1975; 86(2): 225–32PubMedGoogle Scholar
  69. 69.
    Dargan PI, Wallace CI, Jones AL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J 2002; 19(3): 206–9PubMedGoogle Scholar
  70. 70.
    Baud FJ, Borron SW, Bismuth C. Modifying toxicokinetics with antidotes. Toxicol Lett 1995; 82–83: 785–93Google Scholar
  71. 71.
    American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: ipecac syrup. J Toxicol Clin Toxicol 2004; 42(2): 133–43Google Scholar
  72. 72.
    Weaver JE, Griffith JF. Induction of emesis by detergent ingredients and formulations. Toxicol Appl Pharmacol 1969; 14(2): 214–20PubMedGoogle Scholar
  73. 73.
    Chen X, Huang G. Autopsy case report of a rare acute iatrogenic water intoxication with a review of the literature. Forensic Sci Int 1995; 76(1): 27–34PubMedGoogle Scholar
  74. 74.
    American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: gastric lavage. J Toxicol Clin Toxicol 2004; 42(7): 933–43Google Scholar
  75. 75.
    Hoegberg LCG, Angelo HR, Christophersen AB, et al. Effect of ethanol and pH on the adsorption of acetaminophen (paracetamol) to high surface activated charcoal, in vitro studies. J Toxicol Clin Toxicol 2002; 40(1): 59–67PubMedGoogle Scholar
  76. 76.
    Tenenbein PK, Sitar DS, Tenenbein M. Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning. Pharmacotherapy 2001; 21(11): 1331–6PubMedGoogle Scholar
  77. 77.
    Fountain JS. Gastrointestinal decontamination following paraquat ingestion. N Z Med J 2000; 113(1118): 406–7PubMedGoogle Scholar
  78. 78.
    Bismuth C, Garnier R, Baud FJ, et al. Paraquat poisoning: an overview of the current status. Drug Saf 1990 Jul–Aug; 5(4): 243–51PubMedGoogle Scholar
  79. 79.
    American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42(6): 843–54Google Scholar
  80. 80.
    McGuire BW, Sia LL, Haynes JD, et al. Absorption kinetics of orally administered leucovorin calcium. NCI Monogr 1987; (5): 47–56PubMedGoogle Scholar
  81. 81.
    Bressolle F, Kinowski JM, Morel J, et al. Folic acid alters methotrexate availability in patients with rheumatoid arthritis. J Rheumatol 2000; 27(9): 2110–4PubMedGoogle Scholar
  82. 82.
    Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol 2004; 42(1): 1–26PubMedGoogle Scholar
  83. 83.
    Garrettson LK, Geller RJ. Acid and alkaline diuresis: when are they of value in the treatment of poisoning? Drug Saf 1990; 5(3): 220–32PubMedGoogle Scholar
  84. 84.
    Dawson AH. Toxicokinetics and toxicodynamics: the impact of pH change [abstract]. In: XXI International Congress of the European Association of Poisons Centres and Clinical Toxicologists; 2001 May 16–19; Barcelona. J Toxicol Clin Toxicol 2001; 39(3): 210–1Google Scholar
  85. 85.
    American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999; 37(6): 731–51Google Scholar
  86. 86.
    Chyka PA. Multiple-dose activated charcoal and enhancement of systemic drug clearance: summary of studies in animals and human volunteers. J Toxicol Clin Toxicol 1995; 33(5): 399–405PubMedGoogle Scholar
  87. 87.
    Borkan SC. Extracorporeal therapies for acute intoxications. Crit Care Clin 2002; 18(2): 393–420PubMedGoogle Scholar
  88. 88.
    Winchester JF. Dialysis and hemoperfusion in poisoning. Adv Ren Replace Ther 2002; 9(1): 26–30PubMedGoogle Scholar
  89. 89.
    Pond SM. Extracorporeal techniques in the treatment of poisoned patients. Med J Aust 1991; 154(9): 617–22PubMedGoogle Scholar
  90. 90.
    Bironneau E, Garrec F, Kergueris MF, et al. Hemodialfiltration in pentobarbital poisoning. Renal Failure 1996; 18(2): 299–303PubMedGoogle Scholar
  91. 91.
    Berman LB, Jeghers HJ, Schreiner GE, et al. Hemodialysis, an effective therapy for acute barbiturate poisoning. JAMA 1956; 161(9): 820–7Google Scholar
  92. 92.
    Kielstein JT, Schwarz A, Arnavaz A, et al. High-flux hemodialysis — an effective alternative to hemoperfusion in the treatment of carbamazepine intoxication. Clin Nephrol 2002; 57(6): 484–6PubMedGoogle Scholar
  93. 93.
    Groszek B. Hemodialysis, hemofiltration and their modalities in the treatment of acute poisoning. J Toxicol Clin Toxicol 2004; 42(4): 436–8Google Scholar
  94. 94.
    Tapolyai M, Campbell M, Dailey K, et al. Hemodialysis is as effective as hemoperfusion for drug removal in carbamazepine poisoning. Nephron 2002; 90(2): 213–5PubMedGoogle Scholar
  95. 95.
    Vale JA, Rees AJ, Widdop B, et al. Use of charcoal haemoperfusion in the management of severely poisoned patients. BMJ 1975; 1: 5–9PubMedGoogle Scholar
  96. 96.
    Iversen BM, Willassen Y, Bakke OM, et al. Assessment of barbiturate removal by charcoal hemoperfusion in overdose cases. Clin Toxicol 1979; 15(2): 139–49PubMedGoogle Scholar
  97. 97.
    Cohan SL, Winchester JF, Gelfand MC. Treatment of intoxication with charcoal hemadsorption. Drug Metab Rev 1982; 13(4): 681–93PubMedGoogle Scholar
  98. 98.
    Gelfand MC, Winchester JF, Knepshield JH, et al. Treatment of severe drug overdose with charcoal hemoperfusion. Trans Am Soc Artif Internal Organs 1977; 23: 599–605Google Scholar
  99. 99.
    Jaeger A. Developing evidence: molecular adsorbents recirculating system (MARS) as a critical example. Clin Toxicol 2005; 43(5): 440–1Google Scholar
  100. 100.
    Ash SR, Levy H, Akmal M, et al. Treatment of severe tricyclic antidepressant overdose with extracorporeal sorbent detoxification. Adv Ren Replace Ther 2002; 9(1): 31–41PubMedGoogle Scholar
  101. 101.
    Sen S, Ytrebo LM, Rose C, et al. Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs. Intensive Care Med 2004; 30(3): 496–501PubMedGoogle Scholar
  102. 102.
    Nenov VD, Marinov P, Sabeva J, et al. Current applications of plasmapheresis in clinical toxicology. Nephrol Dial Transplant 2003; 18 Suppl. 5: v56–8PubMedGoogle Scholar
  103. 103.
    Flanagan RJ, Jones AL. Fab antibody fragments: some applications in clinical toxicology. Drug Saf 2004; 27(14): 1115–33PubMedGoogle Scholar
  104. 104.
    Eddleston M, Persson H. Acute plant poisoning and antitoxin antibodies. J Toxicol Clin Toxicol 2003; 41(3): 309–15PubMedGoogle Scholar
  105. 105.
    Roberts DM, Buckley NA. Antidotes for acute cardenolide (cardiac glycoside) poisoning. Cochrane Database Syst Rev 2006; (4): CD005490PubMedGoogle Scholar
  106. 106.
    Heard K, Dart RC, Bogdan G, et al. A preliminary study of tricyclic antidepressant (TCA) ovine FAB for TCA toxicity. Clin Toxicol (Phila) 2006; 44(3): 275–81Google Scholar
  107. 107.
    Lalloo DG, Theakston RD. Snake antivenoms. J Toxicol Clin Toxicol 2003; 41(3): 277–90PubMedGoogle Scholar
  108. 108.
    Isbister GK, Graudins A, White J, et al. Antivenom treatment in arachnidism. J Toxicol Clin Toxicol 2003; 41(3): 291–300PubMedGoogle Scholar
  109. 109.
    Buckley NA, Isbister GK, Stokes B, et al. Hyperbaric oxygen for carbon monoxide poisoning: a systematic review and critical analysis of the evidence. Toxicol Rev 2005; 24(2): 75–92PubMedGoogle Scholar
  110. 110.
    Prescott LF, Balali-Mood M, Critchley JA, et al. Diuresis or urinary alkalinisation for salicylate poisoning? BMJ (Clin Res Ed) 1982; 285(6352): 1383–6Google Scholar
  111. 111.
    Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med 2001; 344(6): 424–9PubMedGoogle Scholar
  112. 112.
    Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 1999; 340(11): 832–8PubMedGoogle Scholar
  113. 113.
    Ahmadi M, Khalaf LF, Smith HJ, et al. A dapsone-induced blood dyscrasia in the mouse: evidence for the role of an active metabolite. J Pharm Pharmacol 1996; 48(2): 228–32PubMedGoogle Scholar
  114. 114.
    Malfara WR, Pereira CP, Santos AC, et al. Effects of H (2)-receptor antagonists on dapsone-induced methaemoglobinaemia in rats. Pharmacol Res 2002; 45(4): 269–73PubMedGoogle Scholar
  115. 115.
    Coleman MD, Scott AK, Breckenridge AM, et al. The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man. Br J Clin Pharmacol 1990; 30(5): 761–7PubMedGoogle Scholar
  116. 116.
    Coleman MD, Rhodes LE, Scott AK, et al. The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in dermatitis herpetiformis patients. Br J Clin Pharmacol 1992; 34(3): 244–9PubMedGoogle Scholar
  117. 117.
    Rhodes LE, Tingle MD, Park BK, et al. Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy. Br J Dermatol 1995; 132(2): 257–62PubMedGoogle Scholar
  118. 118.
    Abernethy DR, Greenblatt DJ, Divoll M, et al. Differential effect of cimetidine on drug oxidation (antipyrine and diazepam) vs conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine. J Pharmacol Exp Ther 1983; 224(3): 508–13PubMedGoogle Scholar
  119. 119.
    Buckley N, Eddleston M. Paracetamol (acetaminophen) poisoning. Clin Evid 2002; 7: 1263–9PubMedGoogle Scholar
  120. 120.
    Slikker Jr W, Andersen ME, Bogdanffy MS, et al. Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol Appl Pharmacol 2004; 201(3): 226–94PubMedGoogle Scholar
  121. 121.
    Eddleston M, Wilks MF, Buckley NA. Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review. QJM 2003; 96(11): 809–24PubMedGoogle Scholar
  122. 122.
    Roberts D, Buckley N. Urinary alkalinisation for acute chlorophenoxy herbicide poisoning. Cochrane Database Syst Rev 2007; (1): CD005488PubMedGoogle Scholar
  123. 123.
    Zilker T, Eyer P. 4-dimethylaminophenol (4-DMAP) as an antidote for poisoning by cyanide. In: Brent J, Wallace KL, Burkhart KK, et al., editors. Critical care toxicology: diagnosis and management of the critically poisoned patient. Philadelphia (PA): Elsevier Mosby, 2005: 1609–15Google Scholar
  124. 124.
    Holford NH, Sheiner LB. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 1981; 6(6): 429–53PubMedGoogle Scholar
  125. 125.
    Rowland M. Protein binding and drug clearance. Clin Pharmacokinet 1984; 9 Suppl. 1: 10–7PubMedGoogle Scholar
  126. 126.
    Øie S, Guentert TW, Tozer TN. Effect of saturable binding on the pharmacokinetics of drugs: a simulation. J Pharm Pharmacol 1980; 32(7): 471–7PubMedGoogle Scholar
  127. 127.
    Elo HA, Ylitalo P. Distribution of 2-methyl-4-chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: evidence for the involvement of the central nervous system in their toxicity. Toxicol Appl Pharmacol 1979; 51: 439–46PubMedGoogle Scholar
  128. 128.
    Ylitalo P, Narhi U, Elo HA. Increase in the acute toxicity and brain concentrations of chlorophenoxyacetic acids by probenecid in rats. Gen Pharmacol 1990; 21(5): 811–4PubMedGoogle Scholar
  129. 129.
    Tyynelä K, Elo HA, Ylitalo P. Distribution of the three common chlorophenoxyacetic acid herbicides into the rat brain. Arch Toxicol 1990; 64: 61–5PubMedGoogle Scholar
  130. 130.
    Braunlich H, Bernhardt H, Bernhardt I. Renal handling of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in rats. J Appl Toxicol 1989; 9(4): 255–8PubMedGoogle Scholar
  131. 131.
    van Ravenzwaay B, Pigott G, Leibold E. Absorption, distribution, metabolism and excretion of 4-chloro-2-methylphenoxyacetic acid (MCPA) in rats. Food Chem Toxicol 2004; 42(1): 115–25PubMedGoogle Scholar
  132. 132.
    Elo H. Distribution and elimination of 2-methly-4-chorophenoxyacetic acid (MCPA) in male rats. Acta Pharmacol Toxicol (Copenh) 1976; 39: 58–64Google Scholar
  133. 133.
    Roberts DM, Buckley NA, Eddleston M, et al. Toxicokinetics of MCPA in animals and humans [abstract no. SS6]. 4th Annual Scientific Meeting of the Asia Pacific Association of Medical Toxicology; 2004 Nov 24–26; Manila, 28Google Scholar
  134. 134.
    Schmoldt A, Iwersen S, Schlüter W. Massive ingestion of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA). J Toxicol Clin Toxicol 1997; 35(4): 405–8PubMedGoogle Scholar
  135. 135.
    Friesen EG, Jones GR, Vaughan D. Clinical presentation and management of acute 2,4-D oral ingestion. Drug Saf 1990; 5(2): 155–9PubMedGoogle Scholar
  136. 136.
    Doherty JE, de Soyza N, Kane JJ, et al. Clinical pharmacokinetics of digitalis glycosides. Prog Cardiovasc Dis 1978; 21(2): 141–58PubMedGoogle Scholar
  137. 137.
    Valdes Jr R, Jortani SA. Monitoring of unbound digoxin in patients treated with anti-digoxin antigen-binding fragments: a model for the future? Clin Chem 1998; 44(9): 1883–5PubMedGoogle Scholar
  138. 138.
    Weiss M, Kang W. Inotropic effect of digoxin in humans: mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding. Pharm Res 2004; 21(2): 231–6PubMedGoogle Scholar
  139. 139.
    Flanagan RJ, Meredith TJ, Ruprah M, et al. Alkaline diuresis for acute poisoning with chlorophenoxy herbicides and ioxynil. Lancet 1990; 335(8687): 454–8PubMedGoogle Scholar
  140. 140.
    Furst DE. Practical clinical pharmacology and drug interactions of low-dose methotrexate therapy in rheumatoid arthritis. Br J Rheumatol 1995; 34 Suppl. 2: 20–5PubMedGoogle Scholar
  141. 141.
    Pond SM, Rivory LP, Hampson EC, et al. Kinetics of toxic doses of paraquat and the effects of hemoperfusion in the dog. J Toxicol Clin Toxicol 1993; 31(2): 229–46PubMedGoogle Scholar
  142. 142.
    Roberts DM, Ai P, Kaiyuan Z, et al. Extracorporeal blood purification for acute organophosphorus pesticide poisoning. J Intensive Care Med 2007; 22(2): 124–6PubMedGoogle Scholar
  143. 143.
    Guengerich FP. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 2001; 14(6): 611–50PubMedGoogle Scholar
  144. 144.
    Lotsch J, Skarke C, Tegeder I, et al. Drug interactions with patient-controlled analgesia. Clin Pharmacokinet 2002; 41(1): 31–57PubMedGoogle Scholar
  145. 145.
    Carai MA, Colombo G, Quang LS, et al. Resuscitative treatments on 1,4-butanediol mortality in mice. Ann Emerg Med 2006; 47(2): 184–9PubMedGoogle Scholar
  146. 146.
    Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev 2003; 22(3): 165–90PubMedGoogle Scholar
  147. 147.
    Dawson AH, Whyte IM. Management of dapsone poisoning complicated by methaemoglobinaemia. Med Toxicol Adverse Drug Exp 1989; 4(5): 387–92PubMedGoogle Scholar
  148. 148.
    Chow AY, Murphy SD. Propanil (3,4-dichloropropionanilide)-induced methemoglobin formation in relation to its metabolism in vitro. Toxicol Appl Pharmacol 1975; 33(1): 14–20PubMedGoogle Scholar
  149. 149.
    Singleton SD, Murphy SD. Propanil (3,4-dichloropropionanilide)-induced methemoglobin formation in mice in relation to acylamidase activity. Toxicol Appl Pharmacol 1973; 25(1): 20–9PubMedGoogle Scholar
  150. 150.
    McMillan DC, Freeman JP, Hinson JA. Metabolism of the arylamide herbicide propanil: I. Microsomal metabolism and in vitro methemoglobinemia. Toxicol Appl Pharmacol 1990; 103(1): 90–101PubMedGoogle Scholar
  151. 151.
    Hori Y, Nakajima M, Fujisawa M, et al. Simultaneous determination of propanil, carbaryl and 3,4-dichloroaniline in human serum by HPLC with UV detector following solid phase extraction [in Japanese]. Yakugaku Zasshi 2002; 122(3): 247–51PubMedGoogle Scholar
  152. 152.
    Buckley NA, Whyte IM, Dawson AH. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. J Toxicol Clin Toxicol 1995; 33(3): 199–204PubMedGoogle Scholar
  153. 153.
    Brent J. Current management of ethylene glycol poisoning. Drugs 2001; 61(7): 979–88PubMedGoogle Scholar
  154. 154.
    Karunatilake H, Buckley NA. Severe neurotoxicity following oral meperidine (pethidine) overdose. Clin Toxicol (Phila) 2007; 45(2): 200–1Google Scholar
  155. 155.
    Hershey LA. Meperidine and central neurotoxicity. Ann Intern Med 1983; 98(4): 548–9PubMedGoogle Scholar
  156. 156.
    Bluhm RE, Adedoyin A, McCarver DG, et al. Development of dapsone toxicity in patients with inflammatory dermatoses: activity of acetylation and hydroxylation of dapsone as risk factors. Clin Pharmacol Ther 1999; 65(6): 598–605PubMedGoogle Scholar
  157. 157.
    Zuidema J, Hilbers-Modderman ES, Merkus FW. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet 1986; 11(4): 299–315PubMedGoogle Scholar
  158. 158.
    May DG, Porter JA, Uetrecht JP, et al. The contribution of N-hydroxylation and acetylation to dapsone pharmacokinetics in normal subjects. Clin Pharmacol Ther 1990; 48(6): 619–27PubMedGoogle Scholar
  159. 159.
    May DG, Porter J, Wilkinson GR, et al. Frequency distribution of dapsone N-hydroxylase, a putative probe for P4503A4 activity, in a white population. Clin Pharmacol Ther 1994; 55(5): 492–500PubMedGoogle Scholar
  160. 160.
    Gill HJ, Tingle MD, Park BK. N-hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br J Clin Pharmacol 1995; 40(6): 531–8PubMedGoogle Scholar
  161. 161.
    Shen J, Wanwimolruk S, Purves RD, et al. Model representation of salicylate pharmacokinetics using unbound plasma salicylate concentrations and metabolite urinary excretion rates following a single oral dose. J Pharmacokinet Biopharm 1991; 19(5): 575–95PubMedGoogle Scholar
  162. 162.
    Dahlqvist R, Billing B, Miners JO, et al. Nonlinear metabolic disposition of theophylline. Ther Drug Monit 1984; 6(3): 290–7PubMedGoogle Scholar
  163. 163.
    Tang-Liu DD, Williams RL, Riegelman S. Nonlinear theophylline elimination. Clin Pharmacol Ther 1982; 31(3): 358–69PubMedGoogle Scholar
  164. 164.
    Kadlec GJ, Jarboe CH, Pollard SJ, et al. Acute theophylline intoxication: biphasic first order elimination kinetics in a child. Ann Allergy 1978; 41(6): 337–9PubMedGoogle Scholar
  165. 165.
    Greenberg A, Piraino BH, Kroboth PD, et al. Severe theophylline toxicity: role of conservative measures, antiarrhythmic agents, and charcoal hemoperfusion. Am J Med 1984; 76(5): 854–60PubMedGoogle Scholar
  166. 166.
    Tang-Liu DD, Tozer TN, Riegelman S. Urine flow-dependence of theophylline renal clearance in man. J Pharmacokinet Biopharm 1982; 10(4): 351–64PubMedGoogle Scholar
  167. 167.
    Le Couteur DG, Fraser R, Hilmer S, et al. The hepatic sinusoid in aging and cirrhosis: effects on hepatic substrate disposition and drug clearance. Clin Pharmacokinet 2005; 44(2): 187–200PubMedGoogle Scholar
  168. 168.
    Baud FJ, Megarbane B, Deye N, et al. Clinical review: aggressive management and extracorporeal support for drug-induced cardiotoxicity. Crit Care 2007; 11(2): 207PubMedGoogle Scholar
  169. 169.
    Purkayastha S, Bhangoo P, Athanasiou T, et al. Treatment of poisoning induced cardiac impairment using cardiopulmonary bypass: a review. Emerg Med J 2006; 23(4): 246–50PubMedGoogle Scholar
  170. 170.
    Ohuchi S, Izumoto H, Kamata J, et al. A case of aconitine poisoning saved with cardiopulmonary bypass [in Japanese]. Kyobu Geka 2000; 53(7): 541–4PubMedGoogle Scholar
  171. 171.
    Megarbane B, Leprince P, Deye N, et al. Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest. Intensive Care Med 2007; 33(5): 758–64PubMedGoogle Scholar
  172. 172.
    Rowden AK, Norvell J, Eldridge DL, et al. Acetaminophen poisoning. Clin Lab Med 2006; 26(1): 49–65, viiiPubMedGoogle Scholar
  173. 173.
    Makar AB, Tephly TR. Methanol poisoning in the folate-deficientrat. Nature 1976; 261(5562): 715–6PubMedGoogle Scholar
  174. 174.
    Noker PE, Tephly TR. The role of folates in methanol toxicity. Adv Exp Med Biol 1980; 132: 305–15PubMedGoogle Scholar
  175. 175.
    Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002; 40(4): 415–46PubMedGoogle Scholar
  176. 176.
    Fishman J, Roffwarg H, Hellman L. Disposition of naloxone-7,8,3H in normal and narcotic-dependent men. J Pharmacol Exp Ther 1973; 187(3): 575–80PubMedGoogle Scholar
  177. 177.
    Echizen H, Eichelbaum M. Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet 1986; 11(6): 425–49PubMedGoogle Scholar
  178. 178.
    Gupta SK, Hwang S, Atkinson L, et al. Simultaneous first-order and capacity-limited elimination kinetics after oral administration of verapamil. J Clin Pharmacol 1996; 36(1): 25–34PubMedGoogle Scholar
  179. 179.
    Bianchetti G, Regazzi M, Rondanelli R, et al. Bioavailability of diltiazem as a function of the administered dose. Biopharm Drug Dispos 1991; 12(5): 391–401PubMedGoogle Scholar
  180. 180.
    Mackichan JJ, Pyszczynski DR, Jusko WJ. Dose-dependent disposition of oral propranolol in normal subjects. Biopharm Drug Dispos 1980; 1(4): 159–66PubMedGoogle Scholar
  181. 181.
    Iwamoto K, Watanabe J. Dose-dependent presystemic elimination of propranolol due to hepatic first-pass metabolism in rats. J Pharm Pharmacol 1985; 37(11): 826–8PubMedGoogle Scholar
  182. 182.
    Wong SL, Granneman GR. Modeling of sertindole pharmacokinetic disposition in healthy volunteers in short term doseescalation studies. J Pharm Sci 1998; 87(12): 1629–31PubMedGoogle Scholar
  183. 183.
    Buckley NA, McManus PR. Changes in fatalities due to overdose of anxiolytic and sedative drugs in the UK (1983–1999). Drug Saf 2004; 27(2): 135–41PubMedGoogle Scholar
  184. 184.
    Pentikainen PJ, Neuvonen PJ, Tarpila S, et al. Effect of cirrhosis of the liver on the pharmacokinetics of chlormethiazole. BMJ 1978; 2(6141): 861–3PubMedGoogle Scholar
  185. 185.
    Sivilotti MLA, Yarema MC, Juurlink DN, et al. A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. Ann Emerg Med 2005; 46(3): 263–71PubMedGoogle Scholar
  186. 186.
    Banda PW, Quart BD. The effect of mild alcohol consumption on the metabolism of acetaminophen in man. Res Commun Chem Pathol Pharmacol 1982; 38(1): 57–70PubMedGoogle Scholar
  187. 187.
    Critchley JA, Dyson EH, Scott AW, et al. Is there a place for cimetidine or ethanol in the treatment of paracetamol poisoning? Lancet 1983; I(8338): 1375–6Google Scholar
  188. 188.
    Joshi UM, Thornburg JE. Interactions between cimetidine, methylparathion, and parathion. J Toxicol Environ Health 1986; 19(3): 337–44PubMedGoogle Scholar
  189. 189.
    Costa LG, Richter RJ, Li W-F, et al. Paraoxonase (PON1) as a biomarker of susceptibility for organophosphate toxicity. Biomarkers 2003; 8(1): 1–12PubMedGoogle Scholar
  190. 190.
    Kiderlen D, Eyer P, Worek F. Formation and disposition of diethylphosphoryl-obidoxime, a potent anticholinesterase that is hydrolyzed by human paraoxonase (PON1). Biochem Pharmacol 2005; 69(12): 1853–67PubMedGoogle Scholar
  191. 191.
    Baker Jr EL, Warren M, Zack M, et al. Epidemic malathion poisoning in Pakistan malaria workers. Lancet 1978; I(8054): 31–4Google Scholar
  192. 192.
    Talcott RE, Mallipudi NM, Umetsu N, et al. Inactivation of esterases by impurities isolated from technical malathion. Toxicol Appl Pharmacol 1979; 49(1): 107–12PubMedGoogle Scholar
  193. 193.
    de Morais SM, Wells PG. Enhanced acetaminophen toxicity in rats with bilirubin glucuronyl transferase deficiency. Hepatology 1989; 10(2): 163–7PubMedGoogle Scholar
  194. 194.
    de Morais SM, Uetrecht JP, Wells PG. Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert’s syndrome. Gastroenterology 1992; 102(2): 577–86PubMedGoogle Scholar
  195. 195.
    Jusko WJ, Levy G. Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin. J Pharm Sci 1970; 59(6): 765–72PubMedGoogle Scholar
  196. 196.
    Pritchard JB, Miller DS. Mechanisms mediating renal secretion of organic anions and cations. Physiol Rev 1993; 73(4): 765–96PubMedGoogle Scholar
  197. 197.
    Inui KI, Masuda S, Saito H. Cellular and molecular aspects of drug transport in the kidney. Kidney Int 2000; 58(3): 944–58PubMedGoogle Scholar
  198. 198.
    Tirona RG, Kim RB. Pharmacogenomics of organic anion-transporting polypeptides (OATP). Adv Drug Deliv Rev 2002; 54(10): 1343–52PubMedGoogle Scholar
  199. 199.
    Sakaeda T, Nakamura T, Okumura K. Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs. Pharmacogenomics 2003; 4(4): 397–410PubMedGoogle Scholar
  200. 200.
    Ieiri I, Takane H, Otsubo K. The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin Pharmacokinet 2004; 43(9): 553–76PubMedGoogle Scholar
  201. 201.
    Sauerhoff MW, Braun WH, Blau GE, et al. The dose-dependent pharmacokinetic profile of 2,4,5-trichlorophenoxy acetic acid following intravenous administration to rats. Toxicol Appl Pharmacol 1976; 36(3): 491–501PubMedGoogle Scholar
  202. 202.
    van Ravenzwaay B, Hardwick TD, Needham D, et al. Comparative metabolism of 2,4-dichlorophenoxyacetic acid (2,4-D) in rat and dog. Xenobiotica 2003; 33(8): 805–21PubMedGoogle Scholar
  203. 203.
    Brahmi N, Kouraichi N, Thabet H, et al. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning. Am J Emerg Med 2006; 24(4): 440–3PubMedGoogle Scholar
  204. 204.
    Boldy DA, Vale JA, Prescott LF. Treatment of phenobarbitone poisoning with repeated oral administration of activated charcoal. Q J Med 1986; 61(235): 997–1002PubMedGoogle Scholar
  205. 205.
    Wright JG, Boddy AV. All half-lives are wrong, but some half-lives are useful. Clin Pharmacokinet 2001; 40(4): 237–44PubMedGoogle Scholar
  206. 206.
    Friberg LE, Isbister GK, Hackett LP, et al. The population pharmacokinetics of citalopram after deliberate self-poisoning: a Bayesian approach. J Pharmacokinet Pharmacodyn 2005; 32(3–4): 571–605PubMedGoogle Scholar
  207. 207.
    Aarons L, Toon S, Rowland M. Validation of assay methodology used in pharmacokinetic studies. J Pharmacol Methods 1987; 17(4): 337–46PubMedGoogle Scholar
  208. 208.
    Mohamed F, Senarathna L, Percy A, et al. Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil — a GABAA-gated chloride channel blocker. J Toxicol Clin Toxicol 2004; 42(7): 955–63PubMedGoogle Scholar
  209. 209.
    Bradberry SM, Proudfoot AT, Vale JA. Glyphosate poisoning. Toxicol Rev 2004; 23(3): 159–67PubMedGoogle Scholar
  210. 210.
    Dawson AH, Whyte IM. Therapeutic drug monitoring in drug overdose. Br J Clin Pharmacol 2001; 52 Suppl. 1: 97S–102SPubMedGoogle Scholar
  211. 211.
    Eddieston M, Eyer P, Worek F, et al. Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 2005; 366: 1452–9Google Scholar
  212. 212.
    Sivilotti ML, Good AM, Yarema MC, et al. A new predictor of toxicity following acetaminophen overdose based on pretreatment exposure. Clin Toxicol (Phila) 2005; 43(4): 229–34Google Scholar
  213. 213.
    Little GL, Boniface KS, Love JN. Are one or two dangerous? Sulfonylurea exposure in toddlers. J Emerg Med 2005; 28(3): 305–10PubMedGoogle Scholar
  214. 214.
    Cantrell FL, Clark RF. Determining triage guidelines for unintentional overdoses with sulfonylureas. Clin Toxicol 2005; 43(6): 768Google Scholar
  215. 215.
    Day RO, Graham GG, Bieri D, et al. Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers. Br J Clin Pharmacol 1989; 28(6): 695–702PubMedGoogle Scholar
  216. 216.
    Mégarbane B, Baud F. Poisoning induced coma: toxicokinetic-toxicodynamic relationships. J Toxicol Clin Toxicol 2002; 40(3): 256–8Google Scholar
  217. 217.
    Shannon M. Life-threatening events after theophylline overdose: a 10-year prospective analysis. Arch Intern Med 1999; 159(9): 989–94PubMedGoogle Scholar
  218. 218.
    Sessler CN. Theophylline toxicity: clinical features of 116 consecutive cases. Am J Med 1990; 88(6): 567–76PubMedGoogle Scholar
  219. 219.
    Levy G. Kinetics of pharmacologic activity of succinylcholine in man. J Pharm Sci 1967; 56(12): 1687–8PubMedGoogle Scholar
  220. 220.
    Monro AM. Interspecies comparisons in toxicology: the utility and futility of plasma concentrations of the test substance. Regul Toxicol Pharmacol 1990; 12(2): 137–60PubMedGoogle Scholar
  221. 221.
    Eyer F, Pfab R, Felgenhauer N, et al. Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychopharmacol 2006; 26(3): 325–30PubMedGoogle Scholar
  222. 222.
    Bailey B, McGuigan M. Lithium poisoning from a poison control center perspective. Ther Drug Monit 2000; 22(6): 650–5PubMedGoogle Scholar
  223. 223.
    Reynolds DJ, Aronson JK. ABC of monitoring drug therapy: making the most of plasma drug concentration measurements. BMJ 1993; 306(6869): 48–51PubMedGoogle Scholar
  224. 224.
    Bailey B, Buckley NA, Amre DK. A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose. J Toxicol Clin Toxicol 2004; 42(6): 877–88PubMedGoogle Scholar
  225. 225.
    Battistella M. Fomepizole as an antidote for ethylene glycol poisoning. Ann Pharmacother 2002; 36(6): 1085–9PubMedGoogle Scholar
  226. 226.
    Tenenbein M. Good reasons to publish in clinical toxicology. J Toxicol Clin Toxicol 1998; 36(1–2): 137–8PubMedGoogle Scholar
  227. 227.
    Cooper GM, Le Couteur DG, Richardson D, et al. A randomized clinical trial of activated charcoal for the routine management of oral drug overdose. QJM 2005; 98(9): 655–60PubMedGoogle Scholar
  228. 228.
    Eddleston M, Juszczak E, Buckley NA, et al. Randomised controlled trial of routine single or multiple dose superactivated charcoal for self-poisoning in a region with high mortality. Clin Toxicol 2005; 43(5): 442–3Google Scholar
  229. 229.
    Isbister GK, Friberg LE, Duffull SB. Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose. Intensive Care Med 2006; 32(7): 1060–5PubMedGoogle Scholar
  230. 230.
    Caravati EM, Erdman AR, Scharman EJ, et al. Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2007; 45(1): 1–22Google Scholar
  231. 231.
    Isbister GK, O’Leary MA, Schneider JJ, et al. Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: in vivo and in vitro studies. Toxicon 2007; 49(1): 57–67PubMedGoogle Scholar
  232. 232.
    Carrazza MZ, Carrazza FR, Oga S. Clinical and laboratory parameters in dapsone acute intoxication. Rev Saude Publica 2000; 34(4): 396–401PubMedGoogle Scholar
  233. 233.
    Woodhouse KW, Henderson DB, Charlton B, et al. Acute dapsone poisoning: clinical features and pharmacokinetic studies. Hum Toxicol 1983; 2(3): 507–10PubMedGoogle Scholar
  234. 234.
    Ferguson AJ, Lavery GG. Deliberate self-poisoning with dapsone: a case report and summary of relevant pharmacology and treatment. Anaesthesia 1997; 52(4): 359–63PubMedGoogle Scholar
  235. 235.
    Peter C, Hongwan D, Kupfer A, et al. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol 2000; 56(3): 247–50PubMedGoogle Scholar
  236. 236.
    Garza F. Methylene blue. In: Olson KR, editor. Poisoning & drug overdose. 5th ed. New York: Lange Medical Books/McGraw-Hill, 2007: 473–4Google Scholar
  237. 237.
    Shepherd G, Keyes DC. Methylene blue. In: Dart RC, editor. Medical toxicology. Philadelphia (PA): Lippincott Williams & Wilkins, 2004: 220–3Google Scholar
  238. 238.
    Yamashita M, Hukuda T. The pitfall of the general treatment in acute poisoning [in Japanese]. Kyukyu Igaku 1985; 9(1): 65–71Google Scholar
  239. 239.
    Southgate HJ, Masterson R. Lessons to be learned: a case study approach: prolonged methaemoglobinaemia due to inadvertent dapsone poisoning; treatment with methylene blue and exchange transfusion. J R Soc Health 1999; 119(1): 52–5Google Scholar
  240. 240.
    Berlin G, Brodin B, Hilden JO, et al. Acute dapsone intoxication: a case treated with continuous infusion of methylene blue, forced diuresis and plasma exchange. J Toxicol Clin Toxicol 1984; 22(6): 537–48PubMedGoogle Scholar
  241. 241.
    Elonen E, Neuvonen PJ, Halmekoski J, et al. Acute dapsone intoxication: a case with prolonged symptoms. Clin Toxicol 1979; 14(1): 79–85PubMedGoogle Scholar
  242. 242.
    Neuvonen PJ, Elonen E, Haapanen EJ. Acute dapsone intoxication: clinical findings and effect of oral charcoal and haemodialysis on dapsone elimination. Acta Med Scand 1983; 214(3): 215–20PubMedGoogle Scholar
  243. 243.
    Clarke SFJ, Dargan PI, Jones AL. Naloxone in opioid poisoning: walking the tightrope. Emerg Med J 2005; 22(9): 612–6PubMedGoogle Scholar
  244. 244.
    Chern C-H, Chern T-L, Wang L-M, et al. Continuous flumazenil infusion in preventing complications arising from severe benzodiazepine intoxication. Am J Emerg Med 1998; 16(3): 238–41PubMedGoogle Scholar
  245. 245.
    Brammer G, Gibly R, Walter FG, et al. Continuous intravenous flumazenil infusion for benzodiazepine poisoning. Vet Hum Toxicol 2000; 42(5): 280–1PubMedGoogle Scholar
  246. 246.
    Hojer J, Baehrendtz S, Magnusson A, et al. A placebo-controlled trial of flumazenil given by continuous infusion in severe benzodiazepine overdosage. Acta Anaesthesiol Scand 1991; 35(7): 584–90PubMedGoogle Scholar
  247. 247.
    Roberts DM, Aaron CK. Management of acute organophosphorus pesticide poisoning. BMJ 2007; 334(7594): 629–34PubMedGoogle Scholar
  248. 248.
    Goldfrank L, Weisman RS, Errick JK, et al. A dosing nomogram for continuous infusion intravenous naloxone. Ann Emerg Med 1986; 15(5): 566–70PubMedGoogle Scholar
  249. 249.
    Jaeger A. Changes in the approaches to drug elimination in poisoning over the last 40 years. J Toxicol Clin Toxicol 2004; 42(4): 412–4Google Scholar
  250. 250.
    Proudfoot AT, Krenzelok EP, Vale JA, et al. AACT/EAPCCT position paper on urine alkalinization. J Toxicol Clin Toxicol 2002; 40(3): 310–2Google Scholar
  251. 251.
    Lalonde RL, Deshpande R, Hamilton PP, et al. Acceleration of digoxin clearance by activated charcoal. Clin Pharmacol Ther 1985; 37: 367–71PubMedGoogle Scholar
  252. 252.
    Reissell P, Manninen V. Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin: evidence for intestinal secretion of glycosides. Acta Med Scand Suppl 1982; 668: 88–90PubMedGoogle Scholar
  253. 253.
    Caldwell JH, Caldwell PB, Murphy JW, et al. Intestinal secretion of digoxin in the rat: augmentation by feeding activated charcoal. Naunyn Schmiedebergs Arch Pharmacol 1980; 312(3): 271–5PubMedGoogle Scholar
  254. 254.
    Park GD, Goldberg MJ, Specter R, et al. The effects of activated charcoal on digoxin and digitoxin clearance. Drug Intell Clin Pharm 1985; 19(12): 937–41PubMedGoogle Scholar
  255. 255.
    Ibanez C, Carcas AJ, Frias J, et al. Activated charcoal increases digoxin elimination in patients. Int J Cardiol 1995; 48: 27–30PubMedGoogle Scholar
  256. 256.
    Pond S, Rosenberg J, Benowitz NL, et al. Pharmacokinetics of haemoperfusion for drug overdose. Clin Pharmacokinet 1979; 4(5): 329–54PubMedGoogle Scholar
  257. 257.
    de Silva HA, Fonseka MMD, Pathmeswaran A, et al. Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial. Lancet 2003; 361: 1935–8PubMedGoogle Scholar
  258. 258.
    Proudfoot AT, Krenzelok EP, Brent J, et al. Does urine alkalinization increase salicylate elimination? If so, why? Toxicol Rev 2003; 22(3): 129–36PubMedGoogle Scholar
  259. 259.
    Mohammed Ebid AH, Abdel-Rahman HM. Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose. Ther Drug Monit 2001; 23(3): 209–16Google Scholar
  260. 260.
    Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000; 356(9223): 26–30PubMedGoogle Scholar
  261. 261.
    Curtis J, Greenberg M. Availability of charcoal hemoperfusion in teaching hospitals in three US cities. Clin Toxicol 2005; 43(5): 509–10Google Scholar
  262. 262.
    Shalkham AS, Kirrane BM, Goldfarb D, et al. The availability and use of charcoal hemoperfusion in the treatment of poisoned patients. Clin Toxicol 2005; 43(6): 676–7Google Scholar
  263. 263.
    Johnson CA, Simmons WD. 2006 dialysis of drugs [online]. Madison (WI): Nephrology Pharmacy Associates, Inc. Available from URL: [Accessed 2008 Aug 28]
  264. 264.
    Singh SM, McCormick BB, Mustata S, et al. Extracorporeal management of valproic acid overdose: a large regional experience. J Nephrol 2004; 17(1): 43–9PubMedGoogle Scholar
  265. 265.
    Hicks LK, McFarlane PA. Valproic acid overdose and haemodialysis. Nephrol Dial Transplant 2001; 16(7): 1483–6PubMedGoogle Scholar
  266. 266.
    Bowdle AT, Patel IH, Levy RH, et al. Valproic acid dosage and plasma protein binding and clearance. Clin Pharmacol Ther 1980; 28(4): 486–92PubMedGoogle Scholar
  267. 267.
    Gomez Bellver MJ, Garcia Sanchez MJ, Alonso Gonzalez AC, et al. Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications. J Clin Pharm Ther 1993; 18(3): 191–7Google Scholar
  268. 268.
    Cramer JA, Mattson RH, Bennett DM, et al. Variable free and total valproic acid concentrations in sole- and multi-drug therapy. Ther Drug Monit 1986; 8(4): 411–5PubMedGoogle Scholar
  269. 269.
    Isbister GK, Balit CR, Whyte IM, et al. Valproate overdose: a comparative cohort study of self poisonings. Br J Clin Pharmacol 2003; 55(4): 398–404PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.South Asian Clinical Toxicology Research Collaboration, Medical SchoolAustralian National UniversityCanberraAustralia

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