Advertisement

The Interaction of Anesthetic Agents with Hepatic Microsomal Enzymes

  • James M. Perel
  • Lester C. Mark

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.

Keywords

Drug Metabolism Liver Microsome Anesthetic Agent Chloral Hydrate Enzyme Induction 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ackermann, E., and Heinrich, I., Die Aktivitat der N -und O-Demethylase in der Leber des Menschen. Biochem. Pharmacol. 19, 327 (1970).PubMedCrossRefGoogle Scholar
  2. 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).PubMedCrossRefGoogle Scholar
  3. 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. 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).PubMedGoogle Scholar
  5. 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).PubMedCrossRefGoogle Scholar
  6. 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).PubMedGoogle Scholar
  7. 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).PubMedGoogle Scholar
  8. 8.
    Anders, M. W., Enhancement and inhibition of drug metabolism. Annu. Rev. Pharmacol. 11, 37 (1971).PubMedCrossRefGoogle Scholar
  9. 9.
    Axelrod, J., Biochemical factors in the activation and inactivation of drugs. NaunynSchmiedebergs Arch. Exp. Pathol. Pharmak. 238, 24 (1960).Google Scholar
  10. 10.
    Baekeland, F., and Greene, N. M., Effect of diethyl ether on tissue distribution and metabolism of pentobarbital in rats. Anesthesiology 19, 724 (1958).PubMedCrossRefGoogle Scholar
  11. 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).PubMedCrossRefGoogle Scholar
  12. 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).PubMedCrossRefGoogle Scholar
  13. 13.
    Beckett, A. H., and Triggs, E. J., Enzyme induction in man caused by smoking. Nature (London) 216, 587 (1967).CrossRefGoogle Scholar
  14. 13a.
    Benowitz, N. L., and Meister, W., Pharmacokinetics in patients with cardiac failure. Clin. Pharmacokinet. 1, 389 (1976).PubMedCrossRefGoogle Scholar
  15. 14.
    Berman, M. L., and Bochantin, J. E., Nonspecific stimulation of drug metabolism in rats by methoxyflurane. Anesthesiology 32, 500 (1970).PubMedCrossRefGoogle Scholar
  16. 15.
    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).PubMedCrossRefGoogle Scholar
  17. 16.
    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).PubMedGoogle Scholar
  18. 17.
    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).PubMedCrossRefGoogle Scholar
  19. 17a.
    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).PubMedGoogle Scholar
  20. 18.
    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. 19.
    Breckenridge, A., Clinical implications of enzyme induction. Basic Life Sci. 6, 273 (1975).PubMedGoogle Scholar
  22. 20.
    Breckenridge, A., and Orme, M., Clinical implications of enzyme induction. Ann. N. Y. Acad. Sci. 179, 421 (1971).PubMedCrossRefGoogle Scholar
  23. 21.
    Breckenridge, A., Orme, L. E., Davies, L., Thorgeirsson, S. S., and Davies, D. S., Dose-dependent enzyme induction. Clin. Pharmacol. Ther. 14, 514 (1973).PubMedGoogle Scholar
  24. 22.
    Breimer, D. D., “Pharmacokinetics of Hypnotic Drugs.” Drukkerij-Uitgeverij Brakkenstein, Nijmegen, The Netherlands, 1974.Google Scholar
  25. 23.
    Brodie, B. B., Possible mechanisms of drug-induced tissue lesions. Chem.-Biol. Interact. 3, 247 (1971).PubMedCrossRefGoogle Scholar
  26. 24.
    Brodie, B. B., Gillette, J. R., and LaDu, B. N., Enzymatic mechanisms of drugs and other foreign compounds. Annu. Rev. Biochem. 27, 427 (1958).PubMedCrossRefGoogle Scholar
  27. 24a.
    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).Google Scholar
  28. 25.
    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).PubMedCrossRefGoogle Scholar
  29. 26.
    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).PubMedGoogle Scholar
  30. 27.
    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).Google Scholar
  31. 28.
    Brown, B. R., Jr., and Sagalyn, A. M., Hepatic microsomal enzyme induction by inhalation anesthetics: Mechanism in the rat. Anesthesiology 40, 152 (1974).PubMedCrossRefGoogle Scholar
  32. 29.
    Brown, B. R., Jr., Sipes, I. G., and Sagalyn, A. M., Mechanism of acute hepatic toxicity: Chloroform, halothane and glutathionie. Anesthesiology 41, 554 (1974).PubMedCrossRefGoogle Scholar
  33. 30.
    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).PubMedCrossRefGoogle Scholar
  34. 31.
    Buchthal, F., Svensmark, O., and Schiller, P. J., Clinical and electroencephalographic correlation with serum levels of diphenylhydantoin. Arch. Neurol. (Chicago) 2, 624 (1960).Google Scholar
  35. 32.
    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).PubMedGoogle Scholar
  36. 33.
    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).PubMedCrossRefGoogle Scholar
  37. 34.
    Bush, M. T., and Weller, W. L., Metabolic fate of hexobarbital (HB). Drug Metab. Rev. 1, 249 (1972).CrossRefGoogle Scholar
  38. 35.
    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).PubMedGoogle Scholar
  39. 36.
    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. 37.
    Cascorbi, H. F., and Singh-Amaranth, A. V., Fluroxene toxicity. Anesthesiology 37, 480 (1972).PubMedCrossRefGoogle Scholar
  41. 38.
    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).PubMedGoogle Scholar
  42. 39.
    Cascorbi, H. F., Vesell, E. S., Blake, D. A., and Helrich, M., Halothane biotransformation in man. Ann. N.Y. Acad. Sci. 179, 244 (1971).PubMedCrossRefGoogle Scholar
  43. 40.
    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).PubMedGoogle Scholar
  44. 41.
    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).CrossRefGoogle Scholar
  45. 42.
    Cohen, E. N., Trudell, J. R., Edmunds, H. N., and Watson, E., Urinary metabolites of halothane in man. Anesthesiology 43, 392 (1975).PubMedCrossRefGoogle Scholar
  46. 43.
    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. 44.
    Conney, A. H., Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317 (1967).PubMedGoogle Scholar
  48. 45.
    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. 46.
    Cooksley, W. G. E., and Powell, L. W., Drug metabolism and interaction with particular reference to the liver. Drugs 2, 177 (1971).PubMedCrossRefGoogle Scholar
  50. 46a.
    Cooperman, L. H., Effects of anaesthetics on the splanchnic circulation. Br. J. Anaesth. 44, 967 (1972).PubMedCrossRefGoogle Scholar
  51. 47.
    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).PubMedGoogle Scholar
  52. 48.
    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).CrossRefGoogle Scholar
  53. 48a.
    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).CrossRefGoogle Scholar
  54. 49.
    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).PubMedGoogle Scholar
  55. 50.
    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. 51.
    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).PubMedGoogle Scholar
  57. 52.
    Dayton, P. G., and Perd, J. M., Physiological and physicochemical bases of drug interactions in man. Ann. N.Y. Acad Sci. 179, 67 (1971).PubMedCrossRefGoogle Scholar
  58. 53.
    Dayton, P. G., Pruitt, A. W., Faraj, B. A., and Israili, Z. H., Metabolism and disposition of diazoxide. Drug Metab. Dispos. 3, 226 (1975).PubMedGoogle Scholar
  59. 54.
    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).Google Scholar
  60. 55.
    DiFazio, C. A., and Brown, R. E., Lidocaine metabolism in normal and phenobarbital-pretreated dogs. Anesthesiology 36, 238 (1972).PubMedCrossRefGoogle Scholar
  61. 55a.
    Dutton, G. F., Glucuronide synthesis in-fetal liver and other tissues. Biochem. J. 71, 141 (1959).PubMedGoogle Scholar
  62. 55b.
    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).PubMedCrossRefGoogle Scholar
  63. 56.
    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).Google Scholar
  64. 57.
    Fiserova-Bergerova, V., Changes of fluoride content in bone: An index of drug defluorination in vivo. Anesthesiology 38, 345 (1973).PubMedCrossRefGoogle Scholar
  65. 58.
    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. 59.
    Fleischner, G., and Arias, I. M., Recent advances in bilirubin formation, transport, metabolism and excretion. Am. J. Med. 49, 576 (1970).PubMedCrossRefGoogle Scholar
  67. 60.
    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).PubMedGoogle Scholar
  68. 61.
    Forsman, A., and Ohman, R., On the pharmacokinetics of haloperidol. Nord Psykiatr. Tidsskr. 28, 441 (1974).CrossRefGoogle Scholar
  69. 62.
    Freudenthal, R. I., and Carroll, F. I., Metabolism of certain commonly used barbiturates. Drug Metab. Rev. 2, 265 (1973).PubMedCrossRefGoogle Scholar
  70. 63.
    Garattini, S., Drug-blood levels in human newborns. Abstr. Pharmacol.-Toxicol Program Symp., NIGMS, 1971 (1971).Google Scholar
  71. 64.
    Gault, M. H., Shahidi, N. T., and Barber, V. E., Methemoglobin formation in analgesic nephropathy. Clin. Pharmacol. Ther. 15, 521 (1974).PubMedGoogle Scholar
  72. 65.
    Geddes, I. C., Metabolism of volatile anesthetics. Br. J. Anaesth. 44, 953 (1972).PubMedCrossRefGoogle Scholar
  73. 66.
    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).PubMedCrossRefGoogle Scholar
  74. 67.
    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).PubMedGoogle Scholar
  75. 68.
    Gillette, J. R., Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum. Adv. Pharmacol. 4, 219 (1966).PubMedCrossRefGoogle Scholar
  76. 69.
    Gillette, J. R., Effects of various inducers on electron transport system associated with drug metabolism by liver microsomes. Metab., Clin. Exp. 20, 215 (1971).Google Scholar
  77. 70.
    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).PubMedCrossRefGoogle Scholar
  78. 71.
    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).Google Scholar
  79. 72.
    Gion, H., Yoshimura, N., Holaday, D. A., Bergerova, F. V., and Chase, R. E., Biotransformation of fluorexene in man. Anesthesiology 40, 553 (1974).PubMedCrossRefGoogle Scholar
  80. 73.
    Govier, W. C., Reticuloendothelial cells as the site of sulfanilamide acetylation in the rabbit. J. Pharmacol. Exp. Ther. 150, 305 (1965).PubMedGoogle Scholar
  81. 74.
    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).CrossRefGoogle Scholar
  82. 75.
    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).PubMedCrossRefGoogle Scholar
  83. 76.
    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).PubMedGoogle Scholar
  84. 77.
    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).PubMedGoogle Scholar
  85. 78.
    Greenblatt, D. J., and Shader, R. I., “Benzodiazepines in Clinical Practice.” Raven Press, New York, 1974.Google Scholar
  86. 79.
    Greenblatt, D. J., Shader, R. I., and Koch-Weser, J., Flurazepam hydrochloride. Clin. Pharmacol. Ther. 17, 1 (1975).PubMedGoogle Scholar
  87. 80.
    Greene, N. M., The metabolism of drugs employed in anesthesia. Part II. Anesthesiology 29, 327 (1968).PubMedCrossRefGoogle Scholar
  88. 81.
    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).PubMedGoogle Scholar
  89. 82.
    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).PubMedGoogle Scholar
  90. 83.
    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. 84.
    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).Google Scholar
  92. 85.
    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).PubMedCrossRefGoogle Scholar
  93. 86.
    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).PubMedGoogle Scholar
  94. 87.
    Holcomb, R. R., Gerber, N., and Bush, M. T., The metabolic fate of hexobarbital in the rat. J. Pharmacol. Exp. Ther. 188, 15 (1974).PubMedGoogle Scholar
  95. 88.
    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).PubMedGoogle Scholar
  96. 89.
    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).PubMedCrossRefGoogle Scholar
  97. 90.
    Hucker, H. B., Intermediates in drug metabolism reactions. Drug Metab. Rev. 2, 33 (1973).PubMedCrossRefGoogle Scholar
  98. 91.
    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).PubMedCrossRefGoogle Scholar
  99. 92.
    Imai, Y, and Sato, R., Substrate interaction with hydroxylase system in liver microsomes. Biochem. Biophys. Res. Commun. 22, 620 (1966).CrossRefGoogle Scholar
  100. 93.
    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).Google Scholar
  101. 94.
    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).Google Scholar
  102. 95.
    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).PubMedGoogle Scholar
  103. 96.
    Kappas, A., and Song, C. S., Enzyme induction in the liver. Gastroenterology 55, 731 (1968).PubMedGoogle Scholar
  104. 97.
    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).PubMedCrossRefGoogle Scholar
  105. 98.
    Kato, R., Sex-related differences in drug metabolism. Drug Metab. Rev. 3, 1 (1974).PubMedCrossRefGoogle Scholar
  106. 99.
    Keberle, H., Hoffmann, K., and Bernhard, K., The metabolism of glutethimide (Dori-den). Experientia 18, 105 (1963).CrossRefGoogle Scholar
  107. 100.
    Keeri-Szanto, M., and Pomeroy, J. R., Atmospheric pollution and pentazocme metabolism. Lancet 1, 947 (1971).PubMedCrossRefGoogle Scholar
  108. 101.
    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).CrossRefGoogle Scholar
  109. 101a.
    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).PubMedGoogle Scholar
  110. 102.
    Kolmodin-Hedman, B., Decreased plasma half-life in workers exposed to chlorinated pesticides. Eur. J. Clin. Pharmacol. 5, 195 (1973).CrossRefGoogle Scholar
  111. 103.
    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).PubMedCrossRefGoogle Scholar
  112. 104.
    Kupfer, D., and Rosenfeld, J., A sensitive radioactive assay for hexobarbital hydroxylase in hepatic microsomes. Drug Metab. Disp. 1, 760 (1973).Google Scholar
  113. 105.
    Kutt, H., Interactions of antiepileptic drugs. Epilepsia 16, 393 (1975).PubMedCrossRefGoogle Scholar
  114. 106.
    Kutt, H., Winters, W., Kokenge, R., and McDowell, F., Diphenylhydantoin, metabolism, blood levels and toxicity. Arch. Neurol. (Chicago) 11, 642 (1964).Google Scholar
  115. 107.
    Kutt, H., Wolk, M., Scherman, R., and McDowell, F., Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology 14, 542 (1964).PubMedGoogle Scholar
  116. 108.
    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).CrossRefGoogle Scholar
  117. 109.
    Leibman, K. C., Metabolism of trichloroethylene in liver microsomes 1. Characteristics of the reaction. Mol. Pharmacol. 1, 239 (1965).PubMedGoogle Scholar
  118. 110.
    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).PubMedCrossRefGoogle Scholar
  119. 111.
    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).PubMedCrossRefGoogle Scholar
  120. 112.
    Levy, G., Kinetics of drug action in man. Acta Pharmacol. Toxicol. 29, Suppl. 3, 203 (1971).Google Scholar
  121. 113.
    Lieber, C. S., and DeCarli, L. M., Hepatic microsomes: A new site for ethanol oxidation. J. Clin. Invest. 47, 62a, (1969).Google Scholar
  122. 114.
    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).CrossRefGoogle Scholar
  123. 115.
    Linde, H. W., and Berman, M. L., Non-specific stimulation of drug-metabolizing enzymes by inhalation anesthetic agents. Anesth. Analg. (Cleveland) 50, 656 (1971).Google Scholar
  124. 116.
    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).PubMedCrossRefGoogle Scholar
  125. 117.
    MacDonald, M. G., and Robinson, D. S., Clinical observations of possible barbiturate interference with anticoagulants. J. Am. Med. Assoc. 204, 97 (1968).CrossRefGoogle Scholar
  126. 118.
    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).CrossRefGoogle Scholar
  127. 119.
    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).PubMedCrossRefGoogle Scholar
  128. 120.
    Mark, L. C., Metabolism of barbiturates in man. Clin. Pharmacol. Ther. 4, 504 (1963).Google Scholar
  129. 121.
    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. 122.
    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. 123.
    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).CrossRefGoogle Scholar
  132. 124.
    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).PubMedCrossRefGoogle Scholar
  133. 125.
    Mazze, R. I., Trudell, J. R., and Cousins, M. J., Methoxyflurane metabolism and renal dysfunction: Clinical correlation in man. Anesthesiology 35, 247 (1971).PubMedCrossRefGoogle Scholar
  134. 127.
    Meffin, P., Long, G. J., and Thomas, J., Clearance and metabolism of mepivacaine in the human neonate. Clin. Pharmacol. Ther. 14, 218 (1973).PubMedGoogle Scholar
  135. 128.
    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).CrossRefGoogle Scholar
  136. 129.
    Miller, R. P., Roberts, R. J., and Fischer, L. J., Acetoaminophen elimination kinetics in neonates, children and adults. Clin. Pharmacol. Ther. 19, 284 (1976).PubMedGoogle Scholar
  137. 130.
    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).PubMedCrossRefGoogle Scholar
  138. 131.
    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).PubMedCrossRefGoogle Scholar
  139. 132.
    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).PubMedGoogle Scholar
  140. 133.
    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).PubMedGoogle 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).PubMedCrossRefGoogle Scholar
  142. 134.
    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).PubMedCrossRefGoogle Scholar
  143. 135.
    Orrenius, S., and Ernster, L., Phenobarbital-induced synthesis of the oxidative demethylating enzymes of rat liver microsomes. Biochem. Biophys. Res. Commun. 16, 60 (1964).PubMedCrossRefGoogle Scholar
  144. 136.
    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).Google Scholar
  145. 137.
    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).PubMedGoogle Scholar
  146. 138.
    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).PubMedGoogle Scholar
  147. 139.
    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. 140.
    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).PubMedGoogle Scholar
  149. 141.
    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. 142.
    Peterson, J A, Camphor binding by pseudomonas putida cytochrome P-450. Arch. Biochem. Biophys. 144, 678 (1971).CrossRefGoogle Scholar
  151. 143.
    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. 143a.
    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).PubMedCrossRefGoogle Scholar
  153. 143b.
    Price, H. L., and Pauca, A. L., Effects of anesthesia on the peripheral circulation. Clin. Anesthesiol. 3, 73 (1969).Google Scholar
  154. 144.
    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. 145.
    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).CrossRefGoogle Scholar
  156. 146.
    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).PubMedGoogle Scholar
  157. 147.
    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).PubMedGoogle Scholar
  158. 148.
    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).PubMedCrossRefGoogle Scholar
  159. 148a.
    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).PubMedGoogle Scholar
  160. 149.
    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).CrossRefGoogle Scholar
  161. 150.
    Remmer, H., Die Beschleunigung des Evipanabhause unter der Wirkung von Barbituraten. Naturwissenschaften 45, 189 (1958).CrossRefGoogle Scholar
  162. 151.
    Remmer, H., The role of the liver in drug metabolism. Am. J. Med 49, 617 (1970).PubMedCrossRefGoogle Scholar
  163. 152.
    Remmer, H., Induction of drug metabolizing enzyme system in the liver. Eur. J. Clin. Pharmacol. 5, 116 (1972).CrossRefGoogle Scholar
  164. 153.
    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).PubMedCrossRefGoogle Scholar
  165. 154.
    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).PubMedGoogle Scholar
  166. 155.
    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. 156.
    Robinson, D. S., and Sylwester, D., Interaction of commonly prescribed drugs with warfarin. Ann. Intern. Med 72, 853 (1970).PubMedGoogle Scholar
  168. 157.
    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).PubMedGoogle Scholar
  169. 158.
    Rubin, E., and Lieber, C. S., Hepatic microsomal enzymes in man and rat: Induction and inhibition by ethanol. Science 162, 690 (1968).PubMedCrossRefGoogle Scholar
  170. 159.
    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).PubMedCrossRefGoogle Scholar
  171. 160.
    Rubin, A., Tephly, T. R., and Mannering, G. J., Kinetics of drug metabolism by hepatic microsomes. Biochem. Pharmacol. 13, 1007 (1964).PubMedCrossRefGoogle Scholar
  172. 161.
    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).PubMedCrossRefGoogle Scholar
  173. 162.
    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).CrossRefGoogle Scholar
  174. 163.
    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).PubMedCrossRefGoogle Scholar
  175. 164.
    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).PubMedGoogle Scholar
  176. 165.
    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).PubMedGoogle Scholar
  177. 166.
    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).PubMedCrossRefGoogle Scholar
  178. 167.
    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).CrossRefGoogle Scholar
  179. 168.
    Shahidi, N. T., Acetophenotidin sensitivity. Am. J. Dis. Child. 113, 81 (1967).PubMedGoogle Scholar
  180. 169.
    Shahidi, N. T., Acetophenetidin induced methehemoglobinemia Ann. N. Y. Acad. Sci. 151, 822 (1968).PubMedGoogle Scholar
  181. 170.
    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).PubMedGoogle Scholar
  182. 171.
    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).PubMedGoogle Scholar
  183. 172.
    Sjögvist, F., and von Bahr, C., Interindividual differences in drug oxidation: Clinical importance. Drug Metab. Dispos. 1, 469 (1973).Google Scholar
  184. 173.
    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).CrossRefGoogle Scholar
  185. 174.
    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).PubMedGoogle Scholar
  186. 175.
    Slater, T. F., Necrogenic action of carbon tetrachloride in the rat: A speculative mechanism based on activation. Nature (London) 209, 36 (1966).CrossRefGoogle Scholar
  187. 176.
    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).PubMedCrossRefGoogle Scholar
  188. 177.
    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).PubMedGoogle Scholar
  189. 177a.
    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).PubMedGoogle Scholar
  190. 178.
    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).PubMedCrossRefGoogle Scholar
  191. 179.
    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).PubMedCrossRefGoogle Scholar
  192. 180.
    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).PubMedGoogle Scholar
  193. 181.
    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).CrossRefGoogle Scholar
  194. 182.
    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).PubMedGoogle Scholar
  195. 183.
    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).PubMedCrossRefGoogle Scholar
  196. 183a.
    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).PubMedGoogle Scholar
  197. 184.
    Triggs, E. J., and Nation, R. L., Pharmacokinetics in the aged: A review. J. Pharmacokinet. Biopharm. 3, 387 (1975).PubMedCrossRefGoogle Scholar
  198. 185.
    Trolle, D., Phenobarbitone for low-birth-weight babies. Lancet 2, 1123 (1968).PubMedCrossRefGoogle Scholar
  199. 186.
    Uehleke, H., Extrahepatic microsomal drug metabolism. Proc. Eur. Soc. Study Drug Toxic. 10, 94 (1968).Google Scholar
  200. 187.
    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. 188.
    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).PubMedGoogle Scholar
  202. 189.
    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. 190.
    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).CrossRefGoogle Scholar
  204. 191.
    Van Dyke, R. A., and Wood, C. L., Binding of radioactivity from 14C-labeled halothane in isolated perfused rat livers. Anesthesiology 38, 328 (1973).PubMedCrossRefGoogle Scholar
  205. 192.
    Vesell, E. S., Advances in pharmacogenetics. Prog. Med. Genet. 9, 291 (1973).PubMedGoogle Scholar
  206. 193.
    Vesell, E. S., Factors causing interindividual variations of drug concentrations in blood. Clin. Pharmacol. Ther. 16, 135 (1974).PubMedGoogle Scholar
  207. 194.
    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. 195.
    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).PubMedCrossRefGoogle Scholar
  209. 196.
    Vesell, E. S., and Passananti, G. T., Inhibition of drug metabolism in man Drug Metab. Dispos. 1, 402 (1973).PubMedGoogle Scholar
  210. 197.
    Vest, M. F., and Streiff, R. R., Studies on glucuronide formation in newborn infants and older children. J. Dis. Child. 98, 688 (1959).Google Scholar
  211. 198.
    Wattenberg, L. W., and Leony, J. L., Effects of phenothiazines on protective systems against polycyclic hydrocarbons. Cancer Res. 25, 365 (1965).PubMedGoogle Scholar
  212. 199.
    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).PubMedCrossRefGoogle Scholar
  213. 200.
    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).PubMedGoogle Scholar
  214. 201.
    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. 202.
    Whittaker, J. A., and Price Evans, D. A., Genetic control of phenylbutazone metabolism in man. Br. Med J. 4, 323 (1970).PubMedCrossRefGoogle Scholar
  216. 202a.
    Wilkinson, G. R., and Schenker, S., Letter to the editor. Pharmacokinetics of meperidine in man. Clin. Pharmacol. Ther. 19, 486 (1976).Google Scholar
  217. 202b.
    Wilkinson, G. R., and Shand, D. G., Commentary. A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18, 377 (1975).PubMedGoogle Scholar
  218. 202c.
    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).PubMedGoogle Scholar
  219. 203.
    Williams, R. T., “Detoxification mechanisms.” Wiley, New York, 1959.Google Scholar
  220. 204.
    Zamboni, L., Electron microscopic studies of blood embryogenesis in humans. I. The ultrastructure of the fetal liver. J. Ultrastruct. Res. 12, 509 (1965).PubMedCrossRefGoogle Scholar
  221. 205.
    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).PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1978

Authors and Affiliations

  • James M. Perel
  • Lester C. Mark

There are no affiliations available

Personalised recommendations