Skip to main content

The Interaction of Anesthetic Agents with Hepatic Microsomal Enzymes

  • Chapter
Enzymes in Anesthesiology
  • 351 Accesses

Abstract

Did it ever occur to you that a single dose of any drug would last a lifetime if the body did not have means of handling it? Fortunately, a variety of mechanisms is available to counter any invasion of the body by drugs or other foreign substances. These include distribution to and localization in body tissues, such as storage of unchanged drugs in adipose tissue and elsewhere (a temporizing measure, deferring but not avoiding the need for ultimate disposition), biotransformation mediated by enzymes located prim­arily but not exclusively in liver microsomes, and excretion where appropriate via the kidneys, biliary tract, lungs, skin, and various secretory glands and organs.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ackermann, E., and Heinrich, I., Die Aktivitat der N -und O-Demethylase in der Leber des Menschen. Biochem. Pharmacol. 19, 327 (1970).

    Article  PubMed  CAS  Google Scholar 

  2. Alexanderson, B., Price-Evans, D. A., and Sjögvist, F., Steady-state levels of nortriptyline in twins: Influence of genetic factors and drug therapy. Br. Med. J. 4, 764 (1969).

    Article  PubMed  CAS  Google Scholar 

  3. Altman, P. L., and Dittmer, D. S., eds., “Biological Handbooks: Growth,“ p. 33. Fed. Am. Soc. Exp. Biol., Washington, D.C.

    Google Scholar 

  4. Alvares, A. P., Kapelner, S., Sassa, S., and Kappas, A., Drug metabolism in normal children, lead-poisoned children, and normal adults. Clin. Pharmacol. Ther. 17, 179 (1975).

    PubMed  CAS  Google Scholar 

  5. Alvares, A. P., Parli, C. J., and Mannering, G. J., Induction of drug metabolism. VI. Effects of phenobarbital and 3-methycholanthrene administration on N-demethylating enzyme systems of rough and smooth hepatic microsomes. Biochem. Pharmacol. 22, 1037 (1973).

    Article  PubMed  CAS  Google Scholar 

  6. Alvares, A. P., Schilling, G., Levin, W., and Kuntzman, R., Alteration of the microsomal hemoprotein by 3-methylcholanthrene: Effects of ethionine and actinomycin D. J. Pharmacol. Exp. Ther. 163, 417 (1968).

    PubMed  CAS  Google Scholar 

  7. Alvares, A. P., Schilling, G., Levin, W., Kuntzman, R., Brand, L., and Mark, L. C., Cytochromes P-450 and b5 in human liver microsomes. Clin. Pharmacol. Ther. 10, 655 (1969).

    PubMed  CAS  Google Scholar 

  8. Anders, M. W., Enhancement and inhibition of drug metabolism. Annu. Rev. Pharmacol. 11, 37 (1971).

    Article  PubMed  CAS  Google Scholar 

  9. Axelrod, J., Biochemical factors in the activation and inactivation of drugs. NaunynSchmiedebergs Arch. Exp. Pathol. Pharmak. 238, 24 (1960).

    CAS  Google Scholar 

  10. Baekeland, F., and Greene, N. M., Effect of diethyl ether on tissue distribution and metabolism of pentobarbital in rats. Anesthesiology 19, 724 (1958).

    Article  PubMed  CAS  Google Scholar 

  11. Ballou, D. P., Veeger, C., Van der Hoeven, T. A., and Coon, M. J., Properties of partially purified liver microsomal P-450: Acceptance of two electrons during anaerobic titration. FEBS Lett. 38, 337 (1974).

    Article  PubMed  CAS  Google Scholar 

  12. Baron, J., and Tephly, T. R., Further studies on the relationship of the stimulatory effects of phenobarbital and 3,4-benzpyrene on hepatic synthesis to their effects on hepatic microsomal drug oxidations. Arch. Biochem. Biophys. 139, 410 (1970).

    Article  PubMed  CAS  Google Scholar 

  13. Beckett, A. H., and Triggs, E. J., Enzyme induction in man caused by smoking. Nature (London) 216, 587 (1967).

    Article  CAS  Google Scholar 

  14. Benowitz, N. L., and Meister, W., Pharmacokinetics in patients with cardiac failure. Clin. Pharmacokinet. 1, 389 (1976).

    Article  PubMed  CAS  Google Scholar 

  15. Berman, M. L., and Bochantin, J. E., Nonspecific stimulation of drug metabolism in rats by methoxyflurane. Anesthesiology 32, 500 (1970).

    Article  PubMed  CAS  Google Scholar 

  16. Berman, M. L., Lowe, H. J., Bochantin, J. E., and Hagler, K., Uptake and elimination of methoxyflurane as influenced by enzyme induction in the rat. Anesthesiology 38, 352 (1973).

    Article  PubMed  CAS  Google Scholar 

  17. Blaschke, T. F., Meffin, P. J., Melmon, K. L., and Rowland, M., Influence of acute viral hepatitis on phenytoin kinetics and protein binding. Clin. Pharmacol. Ther. 17, 685 (1975).

    PubMed  CAS  Google Scholar 

  18. Bock, K. W., Krauss, E., and Frohling, W., Regulation of a-aminolevulinic acid synthetase by drugs and steroids in vivo and in perfused rat liver. Eur. J. Biochem. 23, 366 (1971).

    Article  PubMed  CAS  Google Scholar 

  19. Branch, R. A., James, J. A., and Read, A. E., The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic liver disease. Clin. Pharmacol. Ther. 20, 81 (1976).

    PubMed  CAS  Google Scholar 

  20. Brand, L., Mark, L. C., Heiber, S., and Perel, J. M., Interaction between diazepam and diphenylhydantoin. Abstr. Sci. Pap. Annu. Meet. Am. Soc. Anesthesiol., p. 251 (1973).

    Google Scholar 

  21. Breckenridge, A., Clinical implications of enzyme induction. Basic Life Sci. 6, 273 (1975).

    PubMed  CAS  Google Scholar 

  22. Breckenridge, A., and Orme, M., Clinical implications of enzyme induction. Ann. N. Y. Acad. Sci. 179, 421 (1971).

    Article  PubMed  CAS  Google Scholar 

  23. Breckenridge, A., Orme, L. E., Davies, L., Thorgeirsson, S. S., and Davies, D. S., Dose-dependent enzyme induction. Clin. Pharmacol. Ther. 14, 514 (1973).

    PubMed  CAS  Google Scholar 

  24. Breimer, D. D., “Pharmacokinetics of Hypnotic Drugs.” Drukkerij-Uitgeverij Brakkenstein, Nijmegen, The Netherlands, 1974.

    Google Scholar 

  25. Brodie, B. B., Possible mechanisms of drug-induced tissue lesions. Chem.-Biol. Interact. 3, 247 (1971).

    Article  PubMed  CAS  Google Scholar 

  26. Brodie, B. B., Gillette, J. R., and LaDu, B. N., Enzymatic mechanisms of drugs and other foreign compounds. Annu. Rev. Biochem. 27, 427 (1958).

    Article  PubMed  CAS  Google Scholar 

  27. Brodie, B. B., Papper, E. M., and Mark, L. C., Fate of procaine in man and properties of its metabolite diethylaminoethanol. Anesth. Analg. (Cleveland) 29, 29 (1950).

    CAS  Google Scholar 

  28. Brodie, B. B., Reid, W. D., Cho, A. K., Sipes, G., Krishna, G., and Gillette, J. R., Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc. Natl. Acad. Sci. U.S.A. 68, 160 (1971).

    Article  PubMed  CAS  Google Scholar 

  29. Brodie, B. B., Weiner, M., Burns, J. J., Simon, G., and Yale, E. K. Y., The physiological disposition of ethyl biscoumacetate (tromexan) in man and a method of its estimation in biological material. J. Pharmacol. Exp. Ther. 106, 453 (1952).

    PubMed  CAS  Google Scholar 

  30. Brown, B. R., Miller, J. A., and Miller, E. C., The metabolism of methylated aminoazo dyes. IV. Dietary factors enhancing demethylation in vitro. J. Biot. Chem. 209, 211 (1954).

    CAS  Google Scholar 

  31. Brown, B. R., Jr., and Sagalyn, A. M., Hepatic microsomal enzyme induction by inhalation anesthetics: Mechanism in the rat. Anesthesiology 40, 152 (1974).

    Article  PubMed  CAS  Google Scholar 

  32. Brown, B. R., Jr., Sipes, I. G., and Sagalyn, A. M., Mechanism of acute hepatic toxicity: Chloroform, halothane and glutathionie. Anesthesiology 41, 554 (1974).

    Article  PubMed  CAS  Google Scholar 

  33. Brown, B. R., Jr., and Vandam, L. D., A review of current advances in metabolism of inhalation anesthetics. Ann. N.Y. Acad. Sci. 179, 235 (1971).

    Article  PubMed  CAS  Google Scholar 

  34. Buchthal, F., Svensmark, O., and Schiller, P. J., Clinical and electroencephalographic correlation with serum levels of diphenylhydantoin. Arch. Neurol. (Chicago) 2, 624 (1960).

    CAS  Google Scholar 

  35. Burns, J. J., Rose, R. K., Chenkin, T., Goldman, A., Schulert, A., and Brodie, B. B., The physiological disposition of phenylbutazone (butazalodin) in man and a method for its estimation in biological material. J. Pharmacol. Exp. Ther. 109, 346 (1953).

    PubMed  CAS  Google Scholar 

  36. Busfield, D., Child, K. J., Atkinson, R. M., and Tomich, E. G., An effect of phenobarbitone on blood levels of griseofulvin in man. Lancet 2, 1042 (1963).

    Article  PubMed  CAS  Google Scholar 

  37. Bush, M. T., and Weller, W. L., Metabolic fate of hexobarbital (HB). Drug Metab. Rev. 1, 249 (1972).

    Article  CAS  Google Scholar 

  38. Byington, K. H., and Leibman, K. C., Metabolism of trichloroethylene in liver microsomes. II. Identification of the reaction product as chloral hydrate. Mol. Pharmacol 1, 247 (1965).

    PubMed  CAS  Google Scholar 

  39. Cascorbi, H. H., Blake, D. A., and Helrich, M., Halothane biotransformation in mice and man. In “Second Symposium on Cellular Toxicity of Anesthetics” (B. R. Fink, ed.), p. 197 Williams & Wilkins, Baltimore, Maryland, 1972.

    Google Scholar 

  40. Cascorbi, H. F., and Singh-Amaranth, A. V., Fluroxene toxicity. Anesthesiology 37, 480 (1972).

    Article  PubMed  CAS  Google Scholar 

  41. Cascorbi, H. F., Vesell, E. S., Blake, D. A., and Helrich, M., Genetic and environmental influence on halothane metabolism in twins. Clin. Pharmacol. Ther. 12, 50 (1971).

    PubMed  CAS  Google Scholar 

  42. Cascorbi, H. F., Vesell, E. S., Blake, D. A., and Helrich, M., Halothane biotransformation in man. Ann. N.Y. Acad. Sci. 179, 244 (1971).

    Article  PubMed  CAS  Google Scholar 

  43. Castleden, C. M., Kaye, C. M., and Parsons, R. L., The effect of age on plasma levels of propanolol and practolol in man. Br. J. Clin. Pharmacol. 2, 303 (1975).

    PubMed  CAS  Google Scholar 

  44. Chen, W., Vrindten. P. A., Dayton, P. G., and Burns, J. J., Accelerated aminopyrine metabolism in human subjects pretreated with phenylbutazone. Life Sci. 2, 35 (1962).

    Article  Google Scholar 

  45. Cohen, E. N., Trudell, J. R., Edmunds, H. N., and Watson, E., Urinary metabolites of halothane in man. Anesthesiology 43, 392 (1975).

    Article  PubMed  CAS  Google Scholar 

  46. Committee on Problems of Drug Safety of the Drug Research Board, National Academy of Sciences-National Research Council, Report: Application of metabolic data to the evaluation of drugs. Clin. Pharmacol. Ther. 10, 607 (1969).

    Google Scholar 

  47. Conney, A. H., Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317 (1967).

    PubMed  CAS  Google Scholar 

  48. Conney, A. H., Levin, W., Jacobson, M., and Kuntzman, R., Effects of drugs and environmental chemicals on steroid metabolism. Clin. PharmacoL Ther. 14, 727 (1974).

    Google Scholar 

  49. Cooksley, W. G. E., and Powell, L. W., Drug metabolism and interaction with particular reference to the liver. Drugs 2, 177 (1971).

    Article  PubMed  CAS  Google Scholar 

  50. Cooperman, L. H., Effects of anaesthetics on the splanchnic circulation. Br. J. Anaesth. 44, 967 (1972).

    Article  PubMed  CAS  Google Scholar 

  51. Cucinell, S. A., Convey, A. H., Sansur, M. S., and Burns, J. J., Drug interactions in man I. Lowering effect of phenobarbital on plasma levels of bishydroxycoumarin (dicumarol) and diphenylhydantoin (dilantin). Clin. Pharmacol. Ther. 6, 420 (1965).

    PubMed  CAS  Google Scholar 

  52. Cucinell, S. A., Odessky, L., Weiss, M., and Dayton, P. G., The effect of chloral hydrate on bishydroxycoumarin metabolism. J. Am. Med. Assoc. 197, 366 (1966).

    Article  CAS  Google Scholar 

  53. Cumming, J. F., and Mannering, G. J., Effect of phenobarbital administration on the oxygen requirement for hexobarbital metabolism in the isolated, perfused rat liver and in the intact rat. Biochem. Pharmacol. 19, 973 (1970).

    Article  CAS  Google Scholar 

  54. Dasberg, H. H., Van der Kleijn, E., Guelen, P. J. R., and Van Praag, H. M., Plasma concentrations of diazepam and of its metabolite N-desmethyldiazepam in relation to anxiolytic effect. Clin. Pharmacol. Ther. 15, 473 (1974).

    PubMed  CAS  Google Scholar 

  55. Davies, D. S., Gigon, P. L., and Gillette, J. R., Species and sex differences in electron transport systems in liver microsomes and their relationship to ethylmorphine demethylation. Life Sci. 8, Part 2, 85 (1969).

    Google Scholar 

  56. Davis, D. C., Schroeder, D. H., Gram, T. E., Reagan, R. L., and Gillette, J. R., A comparison of the effects of halothane and CC14 on the hepatic drug-metabolizing system. J. Pharmacol. Exp. Ther. 177, 556 (1971).

    PubMed  CAS  Google Scholar 

  57. Dayton, P. G., and Perd, J. M., Physiological and physicochemical bases of drug interactions in man. Ann. N.Y. Acad Sci. 179, 67 (1971).

    Article  PubMed  CAS  Google Scholar 

  58. Dayton, P. G., Pruitt, A. W., Faraj, B. A., and Israili, Z. H., Metabolism and disposition of diazoxide. Drug Metab. Dispos. 3, 226 (1975).

    PubMed  CAS  Google Scholar 

  59. Dettli, L., Spring, P., and Ryter, S., Multiple dose kinetics and drug dosage in patients with kidney disease. Acta Pharmacol. Toxicol. 29, Suppl. 3, 211 (1971).

    CAS  Google Scholar 

  60. DiFazio, C. A., and Brown, R. E., Lidocaine metabolism in normal and phenobarbital-pretreated dogs. Anesthesiology 36, 238 (1972).

    Article  PubMed  CAS  Google Scholar 

  61. Dutton, G. F., Glucuronide synthesis in-fetal liver and other tissues. Biochem. J. 71, 141 (1959).

    PubMed  CAS  Google Scholar 

  62. Epstein, R. M., Deutsch, S., Cooperman, L H., Clement, A. J., and Price, H. L., Splanchnic circulation during halothane anesthesia and hypercapnia in normal man. Anesthesiology 27, 654 (1966).

    Article  PubMed  CAS  Google Scholar 

  63. Estabrook, R. W., Cooper, D. Y., and Rosenthal, O., The light reversible monoxide inhibition of the steroid C21-hydroxylase system of the adrenal cortex. Biochem. J. 338, 741 (1963).

    CAS  Google Scholar 

  64. Fiserova-Bergerova, V., Changes of fluoride content in bone: An index of drug defluorination in vivo. Anesthesiology 38, 345 (1973).

    Article  PubMed  CAS  Google Scholar 

  65. Fish, F., and Wilson, W. D. C., Excretion of cocaine and its metabolites in man. J. Pharm. Pharmacol. 21, Suppl. 1355 (1969).

    Google Scholar 

  66. Fleischner, G., and Arias, I. M., Recent advances in bilirubin formation, transport, metabolism and excretion. Am. J. Med. 49, 576 (1970).

    Article  PubMed  CAS  Google Scholar 

  67. Forrest, F. M., Forrest, I. S., and Serra, M. T., Modification of chlorpromazine metabolism by some other drugs frequently administered to psychiatric patients. Biol. Psychiatry 2, 53 (1970).

    PubMed  CAS  Google Scholar 

  68. Forsman, A., and Ohman, R., On the pharmacokinetics of haloperidol. Nord Psykiatr. Tidsskr. 28, 441 (1974).

    Article  Google Scholar 

  69. Freudenthal, R. I., and Carroll, F. I., Metabolism of certain commonly used barbiturates. Drug Metab. Rev. 2, 265 (1973).

    Article  PubMed  CAS  Google Scholar 

  70. Garattini, S., Drug-blood levels in human newborns. Abstr. Pharmacol.-Toxicol Program Symp., NIGMS, 1971 (1971).

    Google Scholar 

  71. Gault, M. H., Shahidi, N. T., and Barber, V. E., Methemoglobin formation in analgesic nephropathy. Clin. Pharmacol. Ther. 15, 521 (1974).

    PubMed  CAS  Google Scholar 

  72. Geddes, I. C., Metabolism of volatile anesthetics. Br. J. Anaesth. 44, 953 (1972).

    Article  PubMed  CAS  Google Scholar 

  73. Gigon, P. L., Gram, T. E., and Gillette, J. R., Effect of drug substrates on the reduction of hepatic microsomal cytochrome P-450 by NADPH. Biochem. Biophys. Res. Commun. 31, 558 (1968).

    Article  PubMed  CAS  Google Scholar 

  74. Gigon, P. L., Gram, T. E., and Gillette, J. R., Studies on the rate of reduction of hepatic microsomal cytochrome P-450 by reduced nicotinamide adenine dinucleotide phosphate: Effect of drug substrates. Mol. Pharmacol. 5, 109 (1969).

    PubMed  CAS  Google Scholar 

  75. Gillette, J. R., Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum. Adv. Pharmacol. 4, 219 (1966).

    Article  PubMed  CAS  Google Scholar 

  76. Gillette, J. R., Effects of various inducers on electron transport system associated with drug metabolism by liver microsomes. Metab., Clin. Exp. 20, 215 (1971).

    CAS  Google Scholar 

  77. Gillette, J. R., Davis, D. C., and Sasame, H. A., Cytochrome P-450 and its role in drug metabolism. Annu Rev. Pharmacol. 12, 57 (1972).

    Article  PubMed  CAS  Google Scholar 

  78. Gillette, J. R., and Stripp, B., Pre-and postnatal enzyme capacity for drug metabolite production. Fed Proc., Fed Am. Soc. Exp. Biol. 34, 172 (1975).

    CAS  Google Scholar 

  79. Gion, H., Yoshimura, N., Holaday, D. A., Bergerova, F. V., and Chase, R. E., Biotransformation of fluorexene in man. Anesthesiology 40, 553 (1974).

    Article  PubMed  CAS  Google Scholar 

  80. Govier, W. C., Reticuloendothelial cells as the site of sulfanilamide acetylation in the rabbit. J. Pharmacol. Exp. Ther. 150, 305 (1965).

    PubMed  CAS  Google Scholar 

  81. Gram, L. F., Christiansen, J., and Overø, K. F., Pharmacokinetic interaction between neuroleptics and tricyclic antidepressants in the rat. Acta Pharmacol. Toxicol. 35, 223 (1974).

    Article  CAS  Google Scholar 

  82. Gram, L. F., and Overd, K. F., Drug interaction: Inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man Br Med J. 1, 463 (1972).

    Article  PubMed  CAS  Google Scholar 

  83. Gram, L. F., Overd, K. F., and Kirk, L., Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. Am. J. Psychiatry 131, 863 (1974).

    PubMed  CAS  Google Scholar 

  84. Gram, T. E., Guarino, A. M., Schroeder, D. H., and Gillette, J. R., Changes in certain kinetic properties of hepatic microsomal aniline hydroxylase and ethylmorphine demethylase associated with postnatal development and maturation in male rats. Biochem. J. 113, 681 (1969).

    PubMed  CAS  Google Scholar 

  85. Greenblatt, D. J., and Shader, R. I., “Benzodiazepines in Clinical Practice.” Raven Press, New York, 1974.

    Google Scholar 

  86. Greenblatt, D. J., Shader, R. I., and Koch-Weser, J., Flurazepam hydrochloride. Clin. Pharmacol. Ther. 17, 1 (1975).

    PubMed  CAS  Google Scholar 

  87. Greene, N. M., The metabolism of drugs employed in anesthesia. Part II. Anesthesiology 29, 327 (1968).

    Article  PubMed  CAS  Google Scholar 

  88. Hammer, W., Martens, S., and Sjögvist, F., A comparative study of the rate of metabolism of desmethylimipramine, nortriptyline and oxyphenylbutazone in man Clin. Pharmacol. Ther. 10, 44 (1969).

    PubMed  CAS  Google Scholar 

  89. Hayes, M. J., Langman, M. J. S., and Short, A. H., Changes in drug metabolism with increasing age. 2. Phenytoin clearance and protein binding. Br. J. Clin. Pharmacol. 2, 73 (1975).

    PubMed  CAS  Google Scholar 

  90. Heinonen, J., Influence of some drugs on toxicity and rate of metabolism of lidocaine and mepivacaine. Ann. Med. Exp. Biol. Fenn. 44, Suppl. 3, 1 (1966).

    Google Scholar 

  91. Held, V. H., Eisert, R., and Oldershausen, H. F., Pharmakokinetik von Glymidine (Glycodiazin) und Tolbutamid bei akuten und chronischen Leber-Schaden. Arzneim.Forsch. 23, 1801 (1973).

    CAS  Google Scholar 

  92. Hildebrandt, A., Remmer, H., and Estabrook, R. W., Cytochrome P-450 of liver microsomes—one pigment or many. Biochem. Biophys. Res. Commun. 30, 607 (1968).

    Article  PubMed  CAS  Google Scholar 

  93. Hillestad, L., Hansen, T., and Melson, H., Diazepam metabolism in normal man II Serum concentration and clinical effect after oral administration. Clin. Pharmacol. Ther. 16, 485 (1974).

    PubMed  CAS  Google Scholar 

  94. Holcomb, R. R., Gerber, N., and Bush, M. T., The metabolic fate of hexobarbital in the rat. J. Pharmacol. Exp. Ther. 188, 15 (1974).

    PubMed  CAS  Google Scholar 

  95. Holtzman, J. L., Gram, T. E., Gigon, P. L., and Gillette, J. R., The distribution of the components of mixed-function oxidase between the rough and the smooth endoplasmic reticulum of liver cells. Biochem. J. 110, 407 (1968).

    PubMed  CAS  Google Scholar 

  96. Holtzman, J. L., and Rumack, H., The kinetics of ethylmorphine activation of the NADPH-cytochrome P-450 reductase activity of hepatic microsomes from male and female rats. Chem.-Biol. Interact. 3, 279 (1971).

    Article  PubMed  CAS  Google Scholar 

  97. Hucker, H. B., Intermediates in drug metabolism reactions. Drug Metab. Rev. 2, 33 (1973).

    Article  PubMed  CAS  Google Scholar 

  98. Hunter, J., Maxwell, J. D., Carrella, M., Stewart, D. A., and Williams, R., Urinary D-glucaric acid excretion as a test for hapatic enzyme induction in man Lancet 1, 572 (1971).

    Article  PubMed  CAS  Google Scholar 

  99. Imai, Y, and Sato, R., Substrate interaction with hydroxylase system in liver microsomes. Biochem. Biophys. Res. Commun. 22, 620 (1966).

    Article  Google Scholar 

  100. Ioannides, C., and Parke, D. V., The effect of ethanol administration on drug oxidations and possible mechanism of ethnol-barbiturate interactions. Biochem. Soc. Trans. 1, 716 (1973).

    CAS  Google Scholar 

  101. Irvine, R. E., Grove, J., Toseland, P. A., and Trounce, J. R., The effect of age on the hydroxylation of amylobarbitone sodium in man Br J. Clin. PharmacoL 1, 41 (1974).

    CAS  Google Scholar 

  102. Kadar, D., Inaba, T., Endrenyi, L., Johnson, G. E., and Kalow, W., Comparative drug elimination capacity in man-glutethimide, amobarbital, antipyrine and sulfinpyrazone. Clin. Pharmacol. Ther. 14, 552 (1973).

    PubMed  CAS  Google Scholar 

  103. Kappas, A., and Song, C. S., Enzyme induction in the liver. Gastroenterology 55, 731 (1968).

    PubMed  CAS  Google Scholar 

  104. Kater, R. M. H., Roggin, G., Tobon, F., Zieve, P., and Iber, F. L., Increased rate of clearance of drugs from the circulation of alcoholics. Am. J. Med Sci. 258; 35 (1969).

    Article  PubMed  CAS  Google Scholar 

  105. Kato, R., Sex-related differences in drug metabolism. Drug Metab. Rev. 3, 1 (1974).

    Article  PubMed  CAS  Google Scholar 

  106. Keberle, H., Hoffmann, K., and Bernhard, K., The metabolism of glutethimide (Dori-den). Experientia 18, 105 (1963).

    Article  Google Scholar 

  107. Keeri-Szanto, M., and Pomeroy, J. R., Atmospheric pollution and pentazocme metabolism. Lancet 1, 947 (1971).

    Article  PubMed  CAS  Google Scholar 

  108. Klotz, U., Avant, G. R., Hoyumpa, A., Schenker, S., and Wilkinson, G. R., The effects of age and liver disease on the disposition and elimination of diazepam in adult man J. Clin. Invest. 35, 347 (1975).

    Article  Google Scholar 

  109. Klotz, U., McHorse, T. S., Wilkinson, G. R., and Schenker, S., The effect of cirrhosis on the disposition and elimination of meperidine in man Clin. PharmacoL Ther. 16, 667 (1974).

    PubMed  CAS  Google Scholar 

  110. Kolmodin-Hedman, B., Decreased plasma half-life in workers exposed to chlorinated pesticides. Eur. J. Clin. Pharmacol. 5, 195 (1973).

    Article  CAS  Google Scholar 

  111. Kristensen, M., Hansen, J. M., and Skovsted L., The influence of phenobarbital on the half-life of diphenylhydantoin in man. Acta Med Scand 185, 347 (1969).

    Article  PubMed  CAS  Google Scholar 

  112. Kupfer, D., and Rosenfeld, J., A sensitive radioactive assay for hexobarbital hydroxylase in hepatic microsomes. Drug Metab. Disp. 1, 760 (1973).

    CAS  Google Scholar 

  113. Kutt, H., Interactions of antiepileptic drugs. Epilepsia 16, 393 (1975).

    Article  PubMed  CAS  Google Scholar 

  114. Kutt, H., Winters, W., Kokenge, R., and McDowell, F., Diphenylhydantoin, metabolism, blood levels and toxicity. Arch. Neurol. (Chicago) 11, 642 (1964).

    CAS  Google Scholar 

  115. Kutt, H., Wolk, M., Scherman, R., and McDowell, F., Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology 14, 542 (1964).

    PubMed  CAS  Google Scholar 

  116. Lee Son, S., Colella, J. J., Jr., and Brown, B. R., Jr., The effect of phenobarbitone on the metabolism of methoxyflurane to oxalic acid in the rat. Br. J. Anaesth. 44, 1224 (1972).

    Article  Google Scholar 

  117. Leibman, K. C., Metabolism of trichloroethylene in liver microsomes 1. Characteristics of the reaction. Mol. Pharmacol. 1, 239 (1965).

    PubMed  CAS  Google Scholar 

  118. Levi, A. J., Sherlock, S., and Walker, D., Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet 1, 1275 (1968).

    Article  PubMed  CAS  Google Scholar 

  119. Levin, W., Sematinger, E., Jacobson, M., and Kuntzman, R., Destruction of cytochrome P-450 by secobarbital and other barbiturates containing allyl groups. Science 176, 1341 (1972).

    Article  PubMed  CAS  Google Scholar 

  120. Levy, G., Kinetics of drug action in man. Acta Pharmacol. Toxicol. 29, Suppl. 3, 203 (1971).

    CAS  Google Scholar 

  121. Lieber, C. S., and DeCarli, L. M., Hepatic microsomes: A new site for ethanol oxidation. J. Clin. Invest. 47, 62a, (1969).

    Google Scholar 

  122. Lieber, C. S., and DeCarli, L. M., Effect of drug administration on the activity of the hepatic microsomal ethanol cxidizing system. Life Sci. 9, 267 (1970).

    Article  CAS  Google Scholar 

  123. Linde, H. W., and Berman, M. L., Non-specific stimulation of drug-metabolizing enzymes by inhalation anesthetic agents. Anesth. Analg. (Cleveland) 50, 656 (1971).

    CAS  Google Scholar 

  124. Ludwig, B. J., Douglas, J. F., Powell, L. S., Meyer, M., and Berger, F. M., Structures of the major metabolites of meprobamate. J. Med.-Pharm. Chem. 3, 53 (1961).

    Article  PubMed  CAS  Google Scholar 

  125. MacDonald, M. G., and Robinson, D. S., Clinical observations of possible barbiturate interference with anticoagulants. J. Am. Med. Assoc. 204, 97 (1968).

    Article  CAS  Google Scholar 

  126. Marian, A. A., Efron, D. H., and Harris, S. R., Appearance of monohydroxylated chlorphromazine metabolities in the central nervous system. Life Sci. 10, 679 (1971).

    Article  Google Scholar 

  127. Mannering, G. J., Properties of cytochrome P-450 as affected by environmental factors: Qualitative changes due to administration of polycyclic hydrocarbons. Metab. Clin. Exp. 20, 228 (1971).

    Article  PubMed  CAS  Google Scholar 

  128. Mark, L. C., Metabolism of barbiturates in man. Clin. Pharmacol. Ther. 4, 504 (1963).

    CAS  Google Scholar 

  129. Mark, L. C., Brand, L., Heiber, S., and Perel, J. M., Effects of deuteration and optical isomerism on activity of pentobarbitol. Fed. Proc., Fed. Am. Soc. Exp. Biol. 30, 442 (1971).

    Google Scholar 

  130. Mark, L. C., Brand, L., Heiber, S., Smith, D., and Carroll, F. I., Pharmacologic activity and biotransformation of R± and S- barbiturate enantioners in mouse and man. Fed Proc. Fed. Am. Soc. Exp. Biol. 32, 681 (1973).

    Google Scholar 

  131. Marniemi, J., Aitio, A., and Vainio, H., Ethanol induced alteration of microsomal membrane bound enzymes of rat liver in vitro. Acta Pharmacol. Toxicol. 37, 222 (1975).

    Article  CAS  Google Scholar 

  132. Maurer, H. M., Wolff, J. A., Finster, M., Poppers, P. J., Pantuck, E., and Conney, A. H., Reduction in concentration of total serum-bilirubin in offspring of women treated with phenobarbitone during pregnancy. Lancet 2, 122 (1968).

    Article  PubMed  CAS  Google Scholar 

  133. Mazze, R. I., Trudell, J. R., and Cousins, M. J., Methoxyflurane metabolism and renal dysfunction: Clinical correlation in man. Anesthesiology 35, 247 (1971).

    Article  PubMed  CAS  Google Scholar 

  134. Meffin, P., Long, G. J., and Thomas, J., Clearance and metabolism of mepivacaine in the human neonate. Clin. Pharmacol. Ther. 14, 218 (1973).

    PubMed  CAS  Google Scholar 

  135. Melville, K. I., Jordon, G. E., and Douglas, D., Toxic and depressant effects of alcohol given orally in combination with glutethimide or secobarbital. Toxicol. Appt. Pharmacol. 9, 363 (1966).

    Article  CAS  Google Scholar 

  136. Miller, R. P., Roberts, R. J., and Fischer, L. J., Acetoaminophen elimination kinetics in neonates, children and adults. Clin. Pharmacol. Ther. 19, 284 (1976).

    PubMed  CAS  Google Scholar 

  137. Moore, M. R., Battistini, V., Beattie, A. D., and Goldberg, A., The effects of certain barbiturates on the hepatic porphyrin metabolism of rats. Biochem. Pharmacol. 19, 751 (1970).

    Article  PubMed  CAS  Google Scholar 

  138. Morselli, P., Rizzo, M., and Garattini, S., Interaction between phenobarbital and diphenyl-hydantoin in animals and in epileptic patients. Ann. N. Y. Acad. Sci. 179, 88 (1971).

    Article  PubMed  CAS  Google Scholar 

  139. Mueller, G. C., and Miller, J. H., The metabolism of methylated aminoazo dyes. II. Oxidative demethylation by rat liver homogenates. J. Biol. Chem. 202, 579 (1953).

    PubMed  CAS  Google Scholar 

  140. Munson, E. S., Malagodi, M. H., Shields, R. P., Tham, M. K., Bergerova, F. V., Holaday, D. A., Perry, J. C., and Embro, W. J., Fluroxene toxicity induced by phenobarbital. Clin. Pharmacol. Ther. 18, 687 (1975).

    PubMed  CAS  Google Scholar 

  141. A. Nies, A. S., Shand, D. G., and Wilkinson, G. R., Altered hepatic blood flow and drug disposition. Clin. Pharmacokinet. 1, 135 (1976).

    Article  PubMed  CAS  Google Scholar 

  142. O’Malley, K., Crooks, J., Duke, E., and Stevenson, I. H., Effect of age and sex on human drug metabolism Br. Med. J. 3, 607 (1971).

    Article  PubMed  Google Scholar 

  143. Orrenius, S., and Ernster, L., Phenobarbital-induced synthesis of the oxidative demethylating enzymes of rat liver microsomes. Biochem. Biophys. Res. Commun. 16, 60 (1964).

    Article  PubMed  CAS  Google Scholar 

  144. Pantuck, E. J., Hsiao, K. -C., Kaplan, S. A., Kuntzman, R., and Conney, A. H., Effects of enzyme induction on intestinal phenacetin metabolism in the rat. J. Pharmacol. Ther. 191, 45 (1974).

    CAS  Google Scholar 

  145. Pantuck, E. J., Hsiao, K. -C., Maggio, A., Nakamura, K., Kuntzman, R., and Conney, A. H., Effect of cigarette smoking on phenacetin metabolism. Clin. Pharmacol. Ther. 15, 9 (1974).

    PubMed  CAS  Google Scholar 

  146. Pelkonen, O., Kaltiala, E. H., Lanni, T. K. I., and Karki, N. T., Comparison of activities of drug-metabolizing enzymes in human fetal and adult livers. Clin. Pharmacol. Ther. 14, 840 (1973).

    PubMed  CAS  Google Scholar 

  147. Perel, J. M., Brand, L., Heiber, S., and Mark, L. C., Effect of methylphenidate on rate of disappearance of thiopental from plasma. Clin. Res. 20, 411 (1972).

    Google Scholar 

  148. Perel, J. M., O’Brien, L., Black, N. B., Bellward, G. D., and Dayton, P. G., Imipramine and chlorpromazine in hepatic microsomal systems. Adv. Biochem. Psychopharmacol. 9, 201 (1974).

    PubMed  CAS  Google Scholar 

  149. Perel, J. M., Shostak, M., Gann, E., Kantor, S. J., and Glassman, A. H., Pharmacodynamics of imipramine and clinical outcome in depressed patients. In “Pharmacokinetics of Psychoactive Drugs” (L. Gottschalk and S. Marlies, eds.), p. 229. Spectrum, New York, 1975.

    Google Scholar 

  150. Peterson, J A, Camphor binding by pseudomonas putida cytochrome P-450. Arch. Biochem. Biophys. 144, 678 (1971).

    Article  CAS  Google Scholar 

  151. Poland, A., Smith, D., Kuntzman, R., Jacobson, M., and Conney, A. H., Effect of intensive occupational exposure to DDT on phenylbutazone and cortisol metabolism in humans. Clin. Pharmacol. Ther. 11, 725 (1970).

    Google Scholar 

  152. Price, H. L., Deutsch, S., Cooperman, L. H., Clement, A. J., and Epstein, R. M., Splanchnic circulation during cyclopropane anesthesia in normal man. Anesthesiology 26, 312 (1965).

    Article  PubMed  CAS  Google Scholar 

  153. Price, H. L., and Pauca, A. L., Effects of anesthesia on the peripheral circulation. Clin. Anesthesiol. 3, 73 (1969).

    CAS  Google Scholar 

  154. Quinn, G. P., Axelrod, J., and Brodie, B. B., Species and sex differences in metabolism and duration of action of hexobarbital (Evipan). Fed. Proc., Fed. Am. Soc. Exp. Biol. 13, 396 (1954).

    Google Scholar 

  155. Quinn, G. P., Axelrod, J., and Brodie, B. B., Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline. Biochem. Pharmacol. 1, 152 (1958).

    Article  Google Scholar 

  156. Rane, A., Garle, M., Borga, O., and Sjöqvist, F., Plasma disappearance of transplacentally transferred diphenyl hydantoin in the newborn studied by mass fragmentography. Clin. Pharmacol. Ther. 15, 39 (1974).

    PubMed  CAS  Google Scholar 

  157. Reidenberg, M. M., James, M., and Dring, L. G., The rate of procaine hydrolysis in serum of normal subjects and diseased patients. Clin. Pharmacol. Ther. 13, 279 (1972).

    PubMed  CAS  Google Scholar 

  158. Reidenberg, M. M., Kostenbauder, H., and Adams, W., Rate of drug metabolism in obese volunteers before and during starvation and in azotemic patients. Metab. Clin. Exp. 18, 209 (1969).

    Article  PubMed  CAS  Google Scholar 

  159. Reidenberg, M. M., Lowenthal, D. T., Briggs, W., and Gasparo, M., Pentobarbital elimination in patients with poor renal function. Clin. Pharmacol. Ther. 20, 67 (1976).

    PubMed  CAS  Google Scholar 

  160. Reidenberg, M. M., Odar-Cederlof, I., von Bahr, C., Borga, O., and Sjöqvist, F., Protein binding of diphenyl hydantoin and desmethylimipramine in plasma from patients with poor renal function. N. Eng. J. Med 285, 264 (1971).

    Article  CAS  Google Scholar 

  161. Remmer, H., Die Beschleunigung des Evipanabhause unter der Wirkung von Barbituraten. Naturwissenschaften 45, 189 (1958).

    Article  CAS  Google Scholar 

  162. Remmer, H., The role of the liver in drug metabolism. Am. J. Med 49, 617 (1970).

    Article  PubMed  CAS  Google Scholar 

  163. Remmer, H., Induction of drug metabolizing enzyme system in the liver. Eur. J. Clin. Pharmacol. 5, 116 (1972).

    Article  CAS  Google Scholar 

  164. Remmer, H., and Merker, H. J., Effect of drugs on the formation of smooth endoplasmic reticulum and drug-metabolizing enzymes. Ann. N. Y. Acad. Sci. 123, 79 (1965).

    Article  PubMed  CAS  Google Scholar 

  165. Remmer, H., Schenkman, J. B., Estabrook, R. W., Sasame, H.A., Gillette, J., Narasimhulu, S., Cooper, D. Y., and Rosenthal, O., Drug interaction with hepatic microsomal cytochrome. Mol. Pharmacol. 2, 187 (1966).

    PubMed  CAS  Google Scholar 

  166. Robinson, D. S., and Amidon, E. L., Interaction of benzodiazepines with warfarin in man. In “The Benzodiazepines” (S. Garattini, E. Mussini, and L. Randall, eds.) p. 641. Raven Press, New York, 1973.

    Google Scholar 

  167. Robinson, D. S., and Sylwester, D., Interaction of commonly prescribed drugs with warfarin. Ann. Intern. Med 72, 853 (1970).

    PubMed  CAS  Google Scholar 

  168. Rubin, E., Bacchin, P., Gang, H., and Lieber, C. S., Induction and inhibition of hepatic microsomal and mitochondrial enzymes by ethanol. Lab. Invest. 22, 569 (1970).

    PubMed  CAS  Google Scholar 

  169. Rubin, E., and Lieber, C. S., Hepatic microsomal enzymes in man and rat: Induction and inhibition by ethanol. Science 162, 690 (1968).

    Article  PubMed  CAS  Google Scholar 

  170. Rubin, E., Lieber, C. S., Alvares, A. P., Levin, W., and Kuntzman, R., Ethanol binding to hepatic microsomes-its increase by ethanol consumption. Biochem. Pharmacol. 20, 229 (1971).

    Article  PubMed  CAS  Google Scholar 

  171. Rubin, A., Tephly, T. R., and Mannering, G. J., Kinetics of drug metabolism by hepatic microsomes. Biochem. Pharmacol. 13, 1007 (1964).

    Article  PubMed  CAS  Google Scholar 

  172. Sasame, H. A., Castro, J. A., and Gillette, J. R., Studies on the destruction of liver microsomal cytochrome P-450 by carbon tetrachloride administration. Biochem. Pharmacol. 17, 1759 (1968).

    Article  PubMed  CAS  Google Scholar 

  173. Sasame, H. A., and Gillette, J. R., Studies on the inhibitory effects of various substances on drug metabolism by liver microsomes: The effect of nicotinamide in altering the apparent mechanism of inhibition. Biochem. Pharmacol. 19, 1025 (1970).

    Article  Google Scholar 

  174. Sawyer, D. C., Eger, E. I., Bahlman, S. H., Cullen, B. F., and Impelman, D., Concentration dependence of hepatic halothane metabolism. Anesthesiology 34, 230 (1971).

    Article  PubMed  CAS  Google Scholar 

  175. Schenkman, J. B., Cinti, D. L., Moldeus, P. W., and Orrenius, S., Newer aspects of substrate binding to cytochrome P-450. Drug Metab. Dispos. 1, 111 (1973).

    PubMed  CAS  Google Scholar 

  176. Schenkman, J B, Frey, I., Remmer, H., and Estabrook, R. W., Sex differences in drug metabolism by rat liver microsomes. MoL PharmacoL 3, 516 (1967).

    PubMed  CAS  Google Scholar 

  177. Sellers, E. M., and Koch-Weser, J., Kinetics and clinical importance of displacement of warfarin from albumin by acidic drugs. Ann. N. Y. Acad Sci. 179, 213 (1971).

    Article  PubMed  CAS  Google Scholar 

  178. Sellman, R., Kanto, J., Raijola, E., and Pekkarinen, A., Human and animal study on elimination from plasma and metabolism of diazepam after chronic alcohol intake. Acta Pharmacol. Toxicol. 36, 33 (1975).

    Article  CAS  Google Scholar 

  179. Shahidi, N. T., Acetophenotidin sensitivity. Am. J. Dis. Child. 113, 81 (1967).

    PubMed  CAS  Google Scholar 

  180. Shahidi, N. T., Acetophenetidin induced methehemoglobinemia Ann. N. Y. Acad. Sci. 151, 822 (1968).

    PubMed  CAS  Google Scholar 

  181. Shideman, F. E., Kelly, A. R., and Adams, B. J., The role of the liver in the detoxication of thiopental (Pentothal) and two other thiobarbiturates. J. Pharmacol. Exp. Ther. 91, 331 (1947).

    PubMed  CAS  Google Scholar 

  182. Shoeman, D. W., Chaplin, D. W., and Mannering, G. J., Induction of drug metabolism. III. Further evidence for the formation of a new P-450 hemoprotein after treatment of rats with 3-methylcholanthrene. MoL Pharmacol. 5, 412 (1969).

    PubMed  CAS  Google Scholar 

  183. Sjögvist, F., and von Bahr, C., Interindividual differences in drug oxidation: Clinical importance. Drug Metab. Dispos. 1, 469 (1973).

    Google Scholar 

  184. Skrinjaric-Spoljar, M., Mathews, H. B., Engel, J. L., and Casida J. E., Response of hepatic microsomal mixed function oxidase to various types of insecticide chemical synergists administered to mice. Biochem. PharmacoL 20, 1607 (1971).

    Article  CAS  Google Scholar 

  185. Sladek, N. E., and Mannering, G. J., Induction of drug metabolism. I. Differences in the mechanisms by which polycyclic hydrocarbons and phenobarbital produce their inductive effects on microsomal N-demethylating systems. Mol. PharmacoL 5, 174 (1969).

    PubMed  CAS  Google Scholar 

  186. Slater, T. F., Necrogenic action of carbon tetrachloride in the rat: A speculative mechanism based on activation. Nature (London) 209, 36 (1966).

    Article  CAS  Google Scholar 

  187. Smuckler, E. A., Iseri, O. A., and Benditt, E. P., An intracellular defect in protein synthesis induced by carbon tetrachloride. J. Exp. Med. 116, 55 (1962).

    Article  PubMed  CAS  Google Scholar 

  188. Stenger, R. J., and Johnson, E. A., Effects of phenobarbital pretreatment on the response of rat liver to halothane administration. Proc. Soc. Exp. BioL Med 140, 1319 (1972).

    PubMed  CAS  Google Scholar 

  189. Stenson, R. E., Constantino, R. E., and Harrison, D. C., Interrelationships of hepatic blood flow, cardiac output and blood levels of lidocaine in man. Circulation 43, 205 (1971).

    PubMed  CAS  Google Scholar 

  190. Stevenson, I. H., O’Malley, K., Turnbull, M. J., and Ballinger, B. R., The effect of chlorpromazine on drug metabolism. J. Pharm. Pharmacol. 24, 577 (1972).

    Article  PubMed  CAS  Google Scholar 

  191. Stier, A., Kunz, H. W., Walli, A. K., and Schimassek, H., Effects on growth and metabolism of rat liver by halothane and its metabolite trifluoracetate. Biochem. Pharmacol. 21, 2181 (1972).

    Article  PubMed  CAS  Google Scholar 

  192. Strong, J. M., Mayfield, D. E., Atkinson, A. J., Bums, B. C., Raymon F., and Webster, L. T., Jr., Pharmacological activity, metabolism and pharmacokinetics of glycinexylidide. Clin. Pharmacol. Ther. 17, 184 (1975).

    PubMed  CAS  Google Scholar 

  193. Taves, D. R., Fry, B., Freeman, R. B., and Gillies, A. J., Toxicity following methoxyflurane anesthesia. II. Fluoride concentration in nephrotoxicity. J. Am. Med. Assoc. 214, 91 (1970).

    Article  CAS  Google Scholar 

  194. Thomson, P. D., Melmon, K. L., Richardson, J. A., Cohn, K., Steinbounn, W., Cudihee, R., and Rowland, M., Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann. Intern. Med 78, 499 (1973).

    PubMed  CAS  Google Scholar 

  195. Thomson, P. D., Rowland, M., and Melmon K. L., The influence of heart failure, liver disease and renal failure on the disposition of lidocaine in man. Am. Heart J. 82, 417 (1971).

    Article  PubMed  CAS  Google Scholar 

  196. Tokola, O., Pelkonen, O., Karki, N. T., Luoma, P., Kaltiala, E. H., and Larmi, T. K. I., Hepatic drug-oxidizing enzyme systems and urinary d-glucaric acid excretion in patients with congestive heart failure. Br. J. Clin. Pharmacol. 2, 429 (1975).

    PubMed  CAS  Google Scholar 

  197. Triggs, E. J., and Nation, R. L., Pharmacokinetics in the aged: A review. J. Pharmacokinet. Biopharm. 3, 387 (1975).

    Article  PubMed  CAS  Google Scholar 

  198. Trolle, D., Phenobarbitone for low-birth-weight babies. Lancet 2, 1123 (1968).

    Article  PubMed  CAS  Google Scholar 

  199. Uehleke, H., Extrahepatic microsomal drug metabolism. Proc. Eur. Soc. Study Drug Toxic. 10, 94 (1968).

    Google Scholar 

  200. Vajda, F. J. E., Prineas, R. J., and Lovell, R. R. H., Interaction between phenytoin and the benzodiazepines. Br. Med. J.O, 346 (1971).

    Google Scholar 

  201. Van Dam, F. E., and Gribnau-Overkamp, M. J. H., The effect of some sedatives (phenobarbital, glutethimide, chlordiazepoxide, chloral hydrate) on the rate of disappearance of ethyl biscoumacetate from the plasma. Folia Med. Neerl. 10, 141 (1967).

    PubMed  Google Scholar 

  202. Van der Kleijn, E., Van Rossum, J. M., Muskens, E. T. J. M., and Rijntjes, N. V. M., Pharmocokinetics of diazepam in dogs, mice and humans. Acta Pharmacol. Toxicol. 29, Suppl. 3, 109 (1971).

    Google Scholar 

  203. Van Dyke, R. A., Chenoweth, M. B., and Van Poznak, A., Metabolism of volatile anesthetics I. Conversion in vivo of several anesthetics to 14CO2 and chloride. Biochem. Pharmacol. 13, 1239 (1964).

    Article  Google Scholar 

  204. Van Dyke, R. A., and Wood, C. L., Binding of radioactivity from 14C-labeled halothane in isolated perfused rat livers. Anesthesiology 38, 328 (1973).

    Article  PubMed  Google Scholar 

  205. Vesell, E. S., Advances in pharmacogenetics. Prog. Med. Genet. 9, 291 (1973).

    PubMed  CAS  Google Scholar 

  206. Vesell, E. S., Factors causing interindividual variations of drug concentrations in blood. Clin. Pharmacol. Ther. 16, 135 (1974).

    PubMed  CAS  Google Scholar 

  207. Vesell, E. S., Application of pharmacokinetic principles to the elucidation of polygenically controlled differences in drug response. In “Pharmacology and Pharmcokinetics” T. Teorell, R. L. Dedrick, and P. G. Condliffe, eds., p. 261. Plenum, New York, 1975.

    Google Scholar 

  208. Vesell, E. S., and Page, J. G., Genetic control of phenobarbital induced shortening of plasma antipyrine half-lives in man. J. Clin. Invest. 48, 2202 (1969).

    Article  PubMed  CAS  Google Scholar 

  209. Vesell, E. S., and Passananti, G. T., Inhibition of drug metabolism in man Drug Metab. Dispos. 1, 402 (1973).

    PubMed  CAS  Google Scholar 

  210. Vest, M. F., and Streiff, R. R., Studies on glucuronide formation in newborn infants and older children. J. Dis. Child. 98, 688 (1959).

    CAS  Google Scholar 

  211. Wattenberg, L. W., and Leony, J. L., Effects of phenothiazines on protective systems against polycyclic hydrocarbons. Cancer Res. 25, 365 (1965).

    PubMed  CAS  Google Scholar 

  212. Welch, R. M., Cavallito, C. J., and Loh, A., Effect of exposure to cigarette smoke on the metabolism of benzopyrene and acetophenetidin by lung and intestine of rats. Toxicol. Appl. Pharmacol. 23, 749 (1972).

    Article  PubMed  CAS  Google Scholar 

  213. Welch, R. M., Harrison, Y. E., Gommi, B. W., Poppers, P. J., Finster, M., and Conney, A. H., Stimulatory effect of cigarette smoking on the hydroxylation of 3.4-benzpyrene and n-demethylation of 3-methyl-4-monomethylaminoazobenzene by enzymes in human placenta. Clin. Pharmacol. Ther. 10, 100 (1969).

    PubMed  CAS  Google Scholar 

  214. Werk, E. E., Sholiton, L. J., and Olinger, C. P., Int. Congr. Proc. Horm. Steroids 2nd, 1966 Excerpta Med. Found. Ser. No 132 Vol. 3, 301 (1967).

    Google Scholar 

  215. Whittaker, J. A., and Price Evans, D. A., Genetic control of phenylbutazone metabolism in man. Br. Med J. 4, 323 (1970).

    Article  PubMed  CAS  Google Scholar 

  216. Wilkinson, G. R., and Schenker, S., Letter to the editor. Pharmacokinetics of meperidine in man. Clin. Pharmacol. Ther. 19, 486 (1976).

    CAS  Google Scholar 

  217. Wilkinson, G. R., and Shand, D. G., Commentary. A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18, 377 (1975).

    PubMed  CAS  Google Scholar 

  218. Williams, R. L., Blaschke, T. F., Meffin, P. J., Melmon, K. L., and Rowland, M., Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide. Clin. Pharmacol. Ther. 21, 301 (1977).

    PubMed  CAS  Google Scholar 

  219. Williams, R. T., “Detoxification mechanisms.” Wiley, New York, 1959.

    Google Scholar 

  220. Zamboni, L., Electron microscopic studies of blood embryogenesis in humans. I. The ultrastructure of the fetal liver. J. Ultrastruct. Res. 12, 509 (1965).

    Article  PubMed  CAS  Google Scholar 

  221. Zarday, Z., Deery, A., Tellis, I., Soberman, R., and Foldes, F. F., Plasma and red cell cholinesterase activity in uremic patients. Effects of hemodialysis and renal transplantation. J. Med 6, 337 (1975).

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1978 Springer-Verlag New York Inc.

About this chapter

Cite this chapter

Perel, J.M., Mark, L.C. (1978). The Interaction of Anesthetic Agents with Hepatic Microsomal Enzymes. In: Foldes, F.F. (eds) Enzymes in Anesthesiology. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-6248-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-6248-0_9

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-6250-3

  • Online ISBN: 978-1-4612-6248-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics