Skip to main content
SpringerLink
Log in

Ethnic Differences in Drug Metabolism

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Interethnic differences in drug-metabolising capacity may be substantial, and they are sufficiently frequent to warrant attention. Such differences may consist of different mean values of quantitative traits in separate populations, or of different frequency distributions as produced by the occurrence of genetic enzyme variants.

The collection of population data requires the investigation of substantial numbers of subjects. This may be no problem if drug-metabolising enzymes occur in blood or are sufficiently stable in their tissues to allow investigation in vitro. However, if investigations require the use of probe drugs, new efforts are needed to adapt pharmacokinetic methods to make them suitable for population studies. This development of methods is further called for because genetic variants seem to be more easily detected through the assessment of particular metabolites than through the determination of pharmacokinetic parameters of the parent drug.

Many studies with probe drugs comparing different populations have given results that are equivocal in terms of the nature-nurture interplay. However, a set of data with antipyrine has pointed to environmental factors as the principal determinant of differences in metabolising capacity, while data with debrisoquine have indicated monogenically controlled variation of one facet of the cytochrome P-450 system. In several instances, statistically significant differences between population means have been established by testing small numbers of subjects, numbers insufficient to establish distribution patterns that would allow the recognition of genetic polymorphism.

The populations studied range from Greenlanders to South African Blacks, but most comparisons pertain to Caucasians and Orientals.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahmad, S.: The functional roles of cytochrome P-450 mediated systems: Present knowledge and future areas of investigation. Drug Metabolism Reviews 10: 1–14 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Alexanderson, B.: Prediction of steady-state plasma levels of nortriptyline from single oral dose kinetics: A study in twins. European Journal of Clinical Pharmacology 6: 44–53 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Alvan, G.: Individual differences in the disposition of drugs metabolised in the body. Clinical Pharmacokinetics 3: 155–175 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Alvares, A.P.; Kappas, A.; Eiseman, J.L.; Anderson, K.E.; Pantuck, C.B.; Pantuck, E.J.; Hsiao, K.-C.; Garland, W.A. and Conney, A.H.: Intraindividual variation in drug disposition. Clinical Pharmacology and Therapeutics 26: 407–419 (1979a).

    PubMed  CAS  Google Scholar 

  • Alvares, A.P.; Pantuck, E.J.; Anderson, K.E.; Kappas, A. and Conney, A.H.: Regulation of drug metabolism in man by environmental factors. Drug Metabolism Reviews 9: 185–205 (1979b).

    Article  PubMed  CAS  Google Scholar 

  • Andoh, B.; Idle, J.R.; Sloan, T.P.; Smith, R.L. and Woolhouse, N.: Inter-ethnic and inter-phenotype differences, among Ghanaians and Caucasians in the metabolic hydroxylation of Phenytoin. British Journal of Clinical Pharmacology 9: 282P–283P (1980).

    Article  Google Scholar 

  • Andreasen, P.B.; Frøland, A.; Skovsted, L.; Andersen, S.A. and Hauge, M.: Diphenylhydantoin half-life in man and its inhibition by Phenylbutazone: The role of genetic factors. Acta Medica Scandinavica 193: 561–564 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Arnold, K. and Gerber, N.: The rate of decline of diphenylhydantoin in human plasma. Clinical Pharmacology and Therapeutics 11: 121–134 (1969).

    Google Scholar 

  • Balasubramaniam, K.; Lucas, S.B.; Mawer, G.E. and Simons, P.J.: The kinetics of amylobarbitone metabolism in healthy men and women. British Journal of Pharmacology 39: 564–572 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Baty, J.D.; Price Evans, D.A. and Robinson, P.A.: The identification of 6-methoxy 8-aminoquinoline as a metabolite of Primaquine in man. Biomedical Mass Spectrometry 2: 304–306 (1975).

    Article  CAS  Google Scholar 

  • Bennion, L.J. and Li, T.-K.: Alcohol metabolism in American Indians and Whites. Lack of racial differences in metabolic rate and liver alcohol dehydrogenase. New England Journal of Medicine. 294: 9–13 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Bernstein, R.E.. Isoniazid hepatotoxicity and acetylation during tuberculosis chemoprophylaxis. American Review of Respiratory Disease 121: 429–430 (1980).

    Google Scholar 

  • Berry, R.J. and Peters, J.: Heterogeneous heterozygosities in Mus musculus populations. Proceedings of the Royal Society of London; B 197: 485–503 (1977).

    Article  CAS  Google Scholar 

  • Bertilsson, L.; Dengler, H.J.; Eichelbaum, M. and Schulz, H.-U.: Pharmacogenetic covariation of defective N-oxidation of sparteine and 4-hydroxylation of debrisoquine. European Journal of Clinical Pharmacology 17: 153–155 (1980a).

    Article  PubMed  CAS  Google Scholar 

  • Bertilsson, L.; Eichelbaum, M.; Mellström, B.; Säwe, J.; Schulz, H.-U. and Sjöqvist, F.: Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man. Life Sciences 27: 1673–1677 (1980b).

    Article  PubMed  CAS  Google Scholar 

  • Branch, R.A.; Salih, S.Y. and Homeida, M.: Racial differences in drug metabolizing ability: A study with antipyrine in the Sudan. Clinical Pharmacology and Therapeutics 24: 283–286 (1978).

    PubMed  CAS  Google Scholar 

  • Branch, RA. and Shand, D.G.: A re-evaluation of intersubject variation in enzyme induction in man. Clinical Pharmacokinetics 4: 104–110 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Breimer, D.D.: Clinical pharmacokinetics of hypnotics. Clinical Pharmacokinetics 2: 93–109 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Breimer, D.D.: Personal communication (1981).

  • Brown, S.S.; Kalow, W.; Pilz, W.; Whittaker, M. and Woronick, C.L.: The plasma cholinesterases: A new perspective. (For the Commission on Toxicology, IUPAC Section on Clinical Chemistry.) Advances in Clinical Chemistry 22: 1–123 (1981).

    CAS  Google Scholar 

  • Buchanan, N.; Bill, P.; Moodley, G. and Eyberg, C.: The metabolism of phenobarbitone, Phenytoin and antipyrine in black patients. South African Medical Journal 52: 394–395 (1977).

    PubMed  CAS  Google Scholar 

  • Carro-Ciampi, G.; Kadar, D. and Kalow, W.: Distribution of serum paraoxon-hydrolyzing activities in a Canadian population. Canadian Journal of Physiology and Pharmacology 59: 904–907 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Chang, T.; Okerholm, R.A. and Glazko, A.J.: Identification of diphenhydramine (Benadryl®) metabolites in human subjects. Research Communications in Chemical Pathology and Pharmacology 9: 391–404 (1974).

    PubMed  CAS  Google Scholar 

  • Chapron, D.J.; Kramer, P.A. and Mercik, S.A.: Kinetic discrimination of three sulfamethazine acetylation phenotypes. Clinical Pharmacology and Therapeutics 27: 104–113 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Chiba, K.; Ishizaki, T.; Miura, H. and Minagawa, K.: Michaelis-Menten pharmacokinetics of diphenylhydantoin and application in the pediatric age patient. Journal of Pediatrics 96: 479–484 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Clarke, B.C.: The evolution of genetic diversity. Proceedings of the Royal Society of London; B 205: 453–474 (1979).

    Article  CAS  Google Scholar 

  • Cooksley, W.G.E.; Farrell, G.C.; Cash, G.A. and Powell, L.W.: The interaction of cigarette smoking and chronic drug ingestion on human drug metabolism. Clinical and Experimental Pharmacology and Physiology 6: 527–533 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Dam, M.; Larsen, L. and Christiansen, J.: Phenytoin: Ethnic differences in plasma level and clearance-, in Gardner-Thorpe et al. (Eds) Antiepileptic Drug Monitoring, pp. 73–80 (Pittman Medical Publishing, England 1977).

    Google Scholar 

  • Danhof, M. and Breimer, D.D.: Therapeutic drug monitoring in saliva. Clinical Pharmacokinetics 3: 39–57 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Danhof, M.; de Groot-van der Vis, E. and Breimer, D.D.: Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man. Pharmacology 18: 210–223 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Davies, D.S.; Kahn, G.C.; Murray, S.; Brodie, M.J. and Boobis, A.R.: Evidence for an enzymatic defect in the 4-hydroxylation of debrisoquine by human liver. British Journal of Clinical Pharmacology 11: 89–91 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Desai, N.K.; Sheth, U.K.; Mucklow, J.C.; Fraser, H.S.; Bulpitt, C.J.; Jones, S.W. and Dollery, C.T.: Antipyrine clearance in Indian villagers. British Journal of Clinical Pharmacology 9: 387–394 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Dollery, C.T.; Fraser, H.S.; Mucklow, J.C. and Bulpitt, C.K.: Contribution of environmental factors to variability in human drug metabolism. Drug Metabolism Reviews 9: 207–220 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Don, M.M.; Masters, C.J. and Winzor, D.J.: Further evidence for the concept of bovine plasma arylesterase as a lipoprotein. Biochemical Journal 151: 625–630 (1975).

    PubMed  CAS  Google Scholar 

  • Dormandy, T.L.: Free-radical oxidation and antioxidants. Lancet 1: 647–650 (1978).

    Article  PubMed  CAS  Google Scholar 

  • du Souich, P.; McLean, A.J.; Stoeckel, K.; Ohlendorf, D. and Gibaldi, M.: Screening methods using sulfamethazine for determining acetylator phenotype. Clinical Pharmacology and Therapeutics 26: 757–765 (1979).

    PubMed  Google Scholar 

  • Eckerson, H.W.; Romson, J.J. and LaDu, B.M.: Differences in quantitative and qualitative enzymatic properties associated with the human serum paraoxonase polymorphism. American Journal of Human Genetics 31: A46 (1979).

    Google Scholar 

  • Edwards, J.A. and Price Evans, D.A.: Ethanol metabolism in subjects possessing typical and atypical liver alcohol dehydrogenase. Clinical Pharmacology and Therapeutics 8: 824–829 (1967).

    PubMed  CAS  Google Scholar 

  • Eichelbaum, M.: Ein Neuentdeckter Defekt im Arzneimittelstoffwechsel des Menschen: Die Fehlende N-oxydation des Spartein. Habilitationsschrift (Bonn 1975).

  • Eichelbaum, M.; Spannbrucker, N. and Dengler, H.J.: A probable genetic defect of the metabolism of sparteine; in Gorrod (Ed.) Biological Oxidation of Nitrogen, pp. 113–118 (Elsevier/North-Holland Biomedical Press, Amsterdam 1978).

    Google Scholar 

  • Eichelbaum, M.; Spannbrucker, N. and Dengler, H.J.: Influence of the defective metabolism of sparteine on its pharmacokinetics. European Journal of Clinical Pharmacology 16: 189–194 (1979a).

    Article  PubMed  CAS  Google Scholar 

  • Eichelbaum, M.; Spannbrucker, N.; Steincke, B. and Dengler, H.J.: Defective N-oxidation of sparteine in man: A new pharmacogenetic defect. European Journal of Clinical Pharmacology 16: 183–187 (1979b).

    Article  PubMed  CAS  Google Scholar 

  • Ellard, G.A.: Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clinical Pharmacology and Therapeutics 19: 610–625 (1976).

    PubMed  CAS  Google Scholar 

  • Ellard, G.A. and Gammon, P.T.: Pharmacokinetics of isoniazid metabolism in man. Journal of Pharmacokinetics and Biopharmaceutics 4: 83–113 (1976).

    PubMed  CAS  Google Scholar 

  • Ellard, G.A. and Gammon, P.T.: Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid-containing regimens. British Journal of Clinical Pharmacology 4: 5–14 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Endrenyi, L.: Distribution characteristics of selected parameters in a population; in Bozler and van Rossum (Eds) Pharmacokinetics During Drug Development — Data Analysis and Evaluation Techniques, pp.27–28 (Fischer Verlag, Stuttgart 1981).

    Google Scholar 

  • Endrenyi, L.; Inaba, T. and Kalow, W.: Genetic study of amobarbital elimination based on its kinetics in twins. Clinical Pharmacology and Therapeutics 6: 701–714 (1976).

    Google Scholar 

  • Ewing, J.A.; Rouse, B.A.: and Pellizzari, E.D.: Alcohol sensitivity and ethnic background. American Journal of Psychiatry 131: 206–210 (1974).

    PubMed  CAS  Google Scholar 

  • Farris, J.J. and Jones, B.M.: Ethanol metabolism in male American Indians and Whites. Alcoholism: Clinical and Experimental Research 2: 77–81 (1978).

    Article  CAS  Google Scholar 

  • Fecycz, T.D.: Metabolic disposition of Phenytoin in man (Thesis, Toronto 1980).

    Google Scholar 

  • Fenna, D.; Mix, L; Schaefer, O. and Gilbert, J.A.L.: Ethanol metabolism in various racial groups. Canadian Medical Association Journal 105: 472–475 (1971).

    PubMed  CAS  Google Scholar 

  • Flügel, M. and Geldmacher-von Mallinckrodt, M.: Zur Kinetik des Paraoxon-spaltenden Enzyms im menschlichen Serum (EC 3.1.1.2). Klinische Wochenschrift 56: 911–916 (1978).

    Article  PubMed  Google Scholar 

  • Fraser, H.S.; Mucklow, J.C.; Bulpitt, C.J.; Khan, C.; Mould, G. and Dollery, C.T.: Environmental effects on antipyrine half-life in man. Clinical Pharmacology and Therapeutics 22: 799–808 (1977).

    PubMed  CAS  Google Scholar 

  • Fraser, H.S.; Mucklow, J.C.; Bulpitt, C.J.; Kahn, C.; Mould, G. and Dollery, C.T.: Environmental factors affecting antipyrine metabolism in London factory and office workers. British Journal of Clinical Pharmacology 7: 237–243 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Fraser, H.S.; Williams, F.M.; Davies, D.L.; Draffan, G.H. and Davies, D.S.: Amylobarbitone hydroxylation kinetics in small samples of rat and human liver. Xenobiotica 6: 465–472 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Frey, W.A. and Vallee, B.L.: Digitalis metabolism and human liver alcohol dehydrogenase. Proceedings of the National Academy of Sciences, USA 77: 924–927 (1980).

    Article  CAS  Google Scholar 

  • Fukai, M. and Wakasugi, C.: Liver alcohol dehydrogenase in a Japanese population. Japanese Journal of Legal Medicine 26: 46–51 (1972).

    Google Scholar 

  • Gelboin, H.V.: Benzo[α]pyrene metabolism, activation, and carcinogenesis: Role and regulation of mixed-function oxidases and related enzymes. Physiological Reviews 60: 1107–1166 (1980).

    PubMed  CAS  Google Scholar 

  • Geldmacher-von Mallinckrodt, M.; Lindorf, H.H.; Petenyi, M.; Flügel, M.; Fischer, T. and Hiller, T.: Genetisch determinierter Polymorphismus der menschlichen Serum-Paraoxonase (EC 3.1.1.2). Humangenetik 17: 331–335 (1973).

    Google Scholar 

  • Gelehrter, T.D.: Medical progress. Enzyme induction. New Zealand Journal of Medicine 294: 522–526, 589-595, 646-651 (1976).

    Article  CAS  Google Scholar 

  • Gillette, J.R.: Effects of induction of cytochrome P-450 enzymes on the concentration of foreign compounds and their metabolites and on the toxicological effects of these compounds. Drug Metabolism Reviews 10: 59–87 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Goedde, H.W.; Agarwal, D.P. and Benkmann, H.-G.: Pharmacogenetics of Cholinesterase: New variants and suxamethonium sensitivity. Das Ärztliche Laboratorium 25: 219–224 (1979a).

    Google Scholar 

  • Goedde, H.W.; Agarwal, D.P. and Harada, S.: Alcohol metabolizing enzymes: Studies of isozymes in human biopsies and cultured fibroblasts. Clinical Genetics 16: 29–33 (1979b).

    Article  PubMed  CAS  Google Scholar 

  • Goedde, H.W.; Harada, S. and Agarwal, D.P.: Racial differences in alcohol sensitivity: A new hypothesis. Human Genetics 51: 331–334 (1979c).

    Article  PubMed  CAS  Google Scholar 

  • Goldberg, D.M.: The expanding role of microsomal enzyme induction, and its implications for clinical chemistry. Clinical Chemistry 26: 691–699 (1980).

    PubMed  CAS  Google Scholar 

  • Greaves, J.; Evans, D.A.P.; Gillies, H.M.; Fletcher, K.A.; Bunnag, D. and Harinasuta, T.: Plasma kinetics and urinary excretion of Primaquine in man. British Journal of Clinical Pharmacology 10: 399–405 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Greenfield, N.J. and Pietruszko, R.: Two adelhyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochimica et Biophysica Acta 483: 35–45 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Guengerich, F.P.: Isolation and purification of cytochrome P-450, and the existence of multiple forms. Pharmacology and Therapeutics 6: 99–121 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Gurtoo, H.L.; Minowada, J.; Paigen, B.; Parker, N.B. and Hayner. N.T.: Factors influencing the measurement and the reproducibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. Journal of the National Cancer Institute 59: 787–798 (1977).

    PubMed  CAS  Google Scholar 

  • Hanna, J.M.: Metabolic responses of Chinese, Japanese and Europeans to alcohol. Alcoholism: Clinical and Experimental Research 2: 89–92 (1978).

    Article  CAS  Google Scholar 

  • Harada, S.; Agarwal, D.P. and Goedde, H.W.: Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing. Human Genetics 40: 214–220 (1978a).

    Article  Google Scholar 

  • Harada, S.; Agarwal, D.P. and Goedde, H.W.: Isozyme variations in acetaldehyde dehydrogenase (EC. 1.2.1.3) in human tissues. Human Genetics 44: 181–185 (1978b).

    Article  PubMed  CAS  Google Scholar 

  • Harada, S.; Agarwal, D.P. and Goedde, H.W.: Electrophoretic and biochemical studies of human aldehyde dehydrogenase isozymes in various tissues. Life Sciences 26: 1773–1780 (1980a).

    Article  PubMed  CAS  Google Scholar 

  • Harada, S.; Misawa, S.; Agarwal, D.P. and Goedde, H.W.: Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: Isozyme variation and its possible role in alcohol intoxication. American Journal of Human Genetics 32: 8–15 (1980b).

    PubMed  CAS  Google Scholar 

  • Harris, H.; Hopkinson, D.A. and Edwards, Y.H.: Polymorphism and the subunit structure of enzymes: A contribution to the neutralist-selectionist controversy. Proceedings of the National Academy of Sciences, USA 74: 698–701 (1977).

    Article  CAS  Google Scholar 

  • Hetzel, MR.; Law, M.; Keal, E.E.; Sloan, T.P.; Idle, J.R. and Smith, R.L.: Is there a genetic component in bronchial carcinoma in smokers?. Thorax 35: 709 (1980).

    Article  Google Scholar 

  • Hietanen, E.: Modification of hepatic drug metabolizing enzyme activities and their induction by dietary protein. General Pharmacology 11: 443–450 (1980).

    PubMed  CAS  Google Scholar 

  • Idle, J.R.; Mahgoub, A.; Sloan, T.P.; Smith, R.L.; Mbanefo, C.P. and Bababunmi, E.A.: Some observations on the oxidation phenotype status of Nigerian patients presenting with cancer. Cancer Letters 11: 331–338 (1981a).

    Article  PubMed  CAS  Google Scholar 

  • Idle, J.R.; Oates, N.S.; Shah, R.R. and Smith R.L.: Is there a genetic predisposition to phenformin-induced lactic acidosis? British Journal of Clinical Pharmacology 11: 418P–419P (1981b).

    Google Scholar 

  • Idle J.R.; Sloan, T.P.; Smith, R.L. and Wakile, L.A.: Application of the phenotyped panel approach to the detection of polymorphism of drug oxidation in man. British Journal of Pharmacology 66: 430P–432P (1979).

    Google Scholar 

  • Idle, J.R. and Smith, R.L.: Polymorphisms of oxidation at carbon centers of drugs and their clinical significance. Drug Metabolism Reviews 9: 301–317 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Illsley, N.P. and Lamartiniere, C.A.: Prenatal programming of hepatic monoamine oxidase by 5,5-diphenylhydantoin. Biochemical Pharmacology 28: 2585–2590 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Inaba, T.; Lucassen, M. and Kalow, W.: Antipyrine metabolism in the rat by three hepatic monooxygenases. Life Sciences 26: 1977–1983 (1980a).

    Article  PubMed  CAS  Google Scholar 

  • Inaba, T.; Otton, S.V. and Kalow, W.: Deficient metabolism of debrisoquine and sparteine. Clinical Pharmacology and Therapeutics 27: 547–549 (1980b).

    Article  PubMed  CAS  Google Scholar 

  • Inaba, T.; Stewart, D.J. and Kalow, W.: Metabolism of cocaine in man. Clinical Pharmacology and Therapeutics 23: 547–552 (1978).

    PubMed  CAS  Google Scholar 

  • Inaba, T.; Tang, B.K.; Endrenyi, L. and Kalow, W.: Amobarbital — A probe of hepatic drug oxidation in man. Clinical Pharmacology and Therapeutics 20: 439–444 (1976).

    PubMed  CAS  Google Scholar 

  • Inaba, T.D.; Uchino, H.; Kadar, D. and Kalow, W.: Antipyrine metabolites in two populations. Research Communications in Chemical Pathology and Pharmacology 32: 235–244 (1981).

    PubMed  CAS  Google Scholar 

  • Islam, S.I.; Idle, J.R. and Smith, R.L.: The polymorphic 4-hydroxylation of debrisoquine in a Saudi arab population. Xenobiotica 10: 819–825 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Johnson, G.B.: Enzyme polymorphism and metabolism. Polymorphism among enzyme loci is related to metabolic function. Science 184: 28–37 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Kadar, D.; Tang, B.K. and Conn, A.W.: The fate of phenobarbital in near-drowning children at normal and artificially maintained low body temperature. Canadian Anaesthetists’ Society Journal (In press, 1982).

  • Kalow, W.; Endrenyi, L.; Inaba, T.; Kadar, D. and Tang, B.: Pharmacogenetic investigation of amobarbital disposition. Advances in Pharmacology and Therapeutics 6: 31–40 (1978).

    Google Scholar 

  • Kalow, W.; Kadar, D.; Inaba, T. and Tang, B.K.: A case of deficiency of N-hydroxylation of amobarbital. Clinical Pharmacology and Therapeutics 21: 530–535 (1977).

    PubMed  CAS  Google Scholar 

  • Kalow, W.; Otton, S.V.; Kadar, D.; Endrenyi, L. and Inaba, T.: Ethnic difference in drug metabolism: Debrisoquine 4-hydroxylation in Caucasians and Orientals. Canadian Journal of Physiology and Pharmacology 58: 1142–1144 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Kalow, W.; Tang, B.K.; Kadar, D.; Endrenyi, L. and Chan, F.-Y.: A method for studying drug metabolism in populations: Racial differences in amobarbital metabolism. Clinical Pharmacology and Therapeutics 26: 766–776 (1979).

    PubMed  CAS  Google Scholar 

  • Kato, R.: Drug metabolism under pathological and abnormal physiological states in animals and man. Xenobiotica 7: 25–92 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Kellermann, G.H. and Luyten-Kellermann, M.: Antipyrine metabolism in man. Ufe Sciences 23: 2485–2490 (1978).

    CAS  Google Scholar 

  • Khanna, J.M. and Israel, Y.: Ethanol metabolism. International Review of Physiology 21: 275–315 (1980).

    PubMed  CAS  Google Scholar 

  • Klein, H.; Fahrig, H. and Wolf, H.P.: Die Bestimmung der Alkoholdehydrogenase und Glutaminsäure-Oxalessigsäure-Transaminase-Aktivität der menschlichen Leber nach dem Tode. Deutsche Zeitschrift der Gesellschaft für Gerichtliche Medizin 52: 615–629 (1962).

    CAS  Google Scholar 

  • Kotake, A.N. and Funae, Y.: High-performance liquid chromatography technique for resolving multiple forms of hepatic membrane-bound cytochrome P-450. Proceedings of the National Academy of Sciences, USA 77: 6473–6475 (1980).

    Article  CAS  Google Scholar 

  • Kroos-de Haan, M.A. and Noordhoek, J.: Enhancement of antipyrine clearance and induction of antipyrine 4-hydroxylation by 3-methylcholanthrene in rats. British Journal of Pharmacology 68: 120P (1980).

    Google Scholar 

  • Küpfer, A.; Dick, B. and Preisig, R.: Polymorphic mephenytoin hydroxylation in man: A new phenotype in the genetic control of hepatic drug metabolism. Gastroenterology 81: 34 (1981).

    Google Scholar 

  • Lake, R.S.; Pezzutti, M.R.; Kropko, M.L.; Freeman, A.E. and Igel, H.J.: Measurement of benzo(a)pyrene metabolism in human monocytes. Cancer Research 37: 2530–2537 (1977).

    PubMed  CAS  Google Scholar 

  • Li, T.-K.: Enzymology of human alcohol metabolism. Advances in Enzymology 45: 427–483 (1977).

    CAS  Google Scholar 

  • Lieber, C.S.: Metabolism of ethanol and alcoholism: Racial and acquired factors. Annals of Internal Medicine 76: 326–327 (1972).

    PubMed  CAS  Google Scholar 

  • Lindgren, S.; Collste, P.; Norlander, B. and Sjöqvist, F.: Gas Chromatographic assessment of the reproducibility of Phenazone plasma half-life in young healthy volunteers. European Journal of Clinical Pharmacology 7: 381–385 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Lockridge, O.; Mottersnaw-Jackson, N.; Eckerson, H.W. and LaDu, B.N.: Hydrolysis of diacetyimorphine (heroin) by human serum Cholinesterase. Journal of Pharmacology and Experimental Therapeutics 215: 1–8 (1980).

    PubMed  CAS  Google Scholar 

  • Luft, F.C.; Fineberg, N.S.; Miller, J.Z., Rankin, L.I.; Crim, C.E. and Weinberger, M.H.: The effects of age, race and heredity on glomerular filtration rate following volume expansion and contraction in normal man. American Journal of the Medical Sciences 279: 15–24 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Mahgoub, A.; Idle, J.R. and Smith, R.L.: A population and familial study of the defective alicyclic hydroxylation of debrisoquine among Egyptians. Xenobiotica 9: 51–56 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Marinovich, N.; Larsson, O. and Barber, K.: Comparative metabolism rates of ethanol in adults of aboriginal and European descent. Med. J. Australia 1 (Suppl.): 44–46 (April, 1976).

    Google Scholar 

  • Mbanefo, C.; Bababunmi, E.A.; Mahgoub, A.; Sloan, T.P.; Idle, J.R. and Smith, R.L.: A study of the debrisoquine hydroxylation polymorphism in a Nigerian population. Xenobiotica 10: 811–818 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Mellström, B.; Bertilsson, L.; Säwe, J.; Schulz, H.-U. and Sjöqvist, F.: E- and Z-10-hydroxylation of nortriptyline: Relationship to polymorphic debrisoquine hydroxylation. Clinical Pharmacology and Therapeutics 30: 189–193 (1981).

    Article  PubMed  Google Scholar 

  • Mellström, B.; Bertilsson, L.; Traskman, L.; Rollins, D.; Åsberg, M. and Sjöqvist, F.: Intraindividual similarity in the metabolism of amitriptyline and chlorimipramine in depressed patients. Pharmacology 19: 282–289 (1979).

    Article  PubMed  Google Scholar 

  • Mitchell, J.R. and Jollows, D.J.: Metabolic activation of drugs to toxic substances. Gastroenterology 68: 392–410 (1975).

    PubMed  CAS  Google Scholar 

  • Mucklow, J.C.; Caraher, M.T.; Henderson, D.B.; Chapman, P.H.; Roberts, D.F. and Rawlins, M.D.: The relationship between individual dietary constituents and antipyrine metabolism in Indo-Pakistani immigrants to Britain. British Journal of Clinical Pharmacology 13: 481–486 (1982).

    PubMed  CAS  Google Scholar 

  • Mucklow, J.C.; Fraser, H.S.; Bulpitt, C.J.; Kahn, C.; Mould, C. and Dollery, C.T.: Environmental factors affecting paracetamol metabolism in London factory and office workers. British Journal of Clinical Pharmacology 10: 67–74 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D.W.: Genetic aspects of enzyme induction by drugs and chemical carcinogens; in Estabrook and Lindenlaub (Eds) The Induction of Drug Metabolism, pp. 419–452 (Schattauer Verlag, Stuttgart 1978).

    Google Scholar 

  • Nebert, D.W.: Genetic differences in the induction of monooxygenase activities by polycyclic aromatic compounds. Pharmacology and Therapeutics 6: 395–417 (1979a).

    Article  CAS  Google Scholar 

  • Nebert, D.W.: Multiple forms of inducible drug-metabolizing enzymes: A reasonable mechanism by which any organism can cope with adversity. Molecular and Cellular Biochemistry 27: 27–46 (1979b).

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D.W.: Human genetic variation in the enzymes of detoxification; in Jakoby (Ed.) Enzymatic Basis of Detoxication, pp. 25–68 (Academic Press, New York 1980).

    Google Scholar 

  • Nebert, D.W.: Clinical pharmacology. Possible clinical importance of genetic differences in drug metabolism. British Medical Journal 283: 537–541 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Nei, M. and Roychoudhury, A.K.: Genetic variation within and between the three major races of man, Caucasoids, Negroids and Mongoloids. American Journal of Human Genetics 26: 421–443 (1974).

    PubMed  CAS  Google Scholar 

  • Nunn, M.A.K.: In vitro studies of antipyrine and amobarbital biotransformation. (Thesis, 1979).

  • Omenn, G.S.: Genetic and environmental interaction in health. National Academy of Sciences/Institute of Medicine Planning Study of US Health Goals for the Year 2000, Appendix C, pp.1–20 (1981).

    Google Scholar 

  • Otton, S.V.; Inaba, T.; Manon, W.A. and Kalow, W.: In vitro metabolism of sparteine by human liver: Competitive inhibition by debrisoquine. Canadian Journal of Physiology and Pharmacology 60: 102–105 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Playfer, J.R.; Eze, L.C.; Bullen, M.F. and Evans, D.A.P.: Genetic polymorphism and interethnic variability of plasma paraoxonase activity. Journal of Medical Genetics 13: 337–342 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.: Kinetics and metabolism of paracetamol and phenacetin. British Journal of Clinical Pharmacology 10: 291S–298S (1980).

    Article  PubMed  Google Scholar 

  • Price Evans, D.A.: Genetic studies involving drug metabolism in man; in Gorrod and Beckett (Eds) Drug Metabolism in Man, pp. 135–155 (Taylor and Francis, London 1978).

    Google Scholar 

  • Price Evans, D.A.; Mahgoub, A.; Sloan, T.P.; Idle, J.R. and Smith R.L.: A family and population study of the genetic polymorphism of debrisoquine oxidation in a White British population. Journal of Medical Genetics 17: 102–105 (1980).

    Article  Google Scholar 

  • Price Evans, D.A.; Manley, K.A. and McKusick, V.A.: Genetic control of isoniazid metabolism in man. British Medical Journal 2: 485–491 (1960).

    Article  Google Scholar 

  • Propping, P.: Pharmacogenetics. Reviews in Physiology, Biochemistry and Pharmacology 83: 124–173 (1978).

    Google Scholar 

  • Rainsford, K.D.; Ford, N.L.V.; Brooks, P.M. and Watson, H.M.: Plasma aspirin esterases in normal individuals, patients with alcoholic liver disease and rheumatoid arthritis; Characterization and the importance of the enzymic components. European Journal of Clinical Investigation 10: 413–420 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Rambeck, B.; Boenigk, H.E.; Dunlop, A.; Mullen, P.W.; Wadsworth, J. and Richens, A.: Predicting Phenytoin dose —a revised nomogram. Therapeutic Drug Monitoring 1: 325–333 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Rao, P.R. and Gopalam, K.B.: High incidence of the silent allele at Cholinesterase locus I in Vysyas of Andhra Pradesh (S. India). Human Genetics 52: 139–141 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Reed, T.E.: Racial comparisons of alcohol metabolism: Background, problems, and results. Alcoholism: Clinical and Experimental Research 2: 83–87 (1978).

    Article  CAS  Google Scholar 

  • Reed, T.E. and Kalant, H.: Bias in calculated rate of alcohol metabolism due to variation in relative amounts of adipose tissue. Journal of Studies on Alcohol 38: 1773–1776 (1977).

    PubMed  CAS  Google Scholar 

  • Reed, T.E; Kalant, H.; Gibbins, R.J.; Kapur, B.M. and Rankin, J.G.: Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds. Canadian Medical Association Journal 115: 851 (1976).

    PubMed  CAS  Google Scholar 

  • Reilly, P.A.J.: Amobarbital biotransformation in different species (Thesis, 1978).

  • Renton, K.W.; Aranda, J.V. and Eade, N.R.: NADPH- dependent lipid peroxidation and its effects on aminopyrine N-demethylation in subcellular fractions of human neonatal liver. Canadian Journal of Physiology and Pharmacology. 54: 838–843 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Richter, A.; Kadar, D.; Liszka-Hagmajer, E. and Kalow, W.; Seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes in culture. Research Communications in Chemical Pathology and Pharmacology 19: 453–475 (1978).

    PubMed  CAS  Google Scholar 

  • Ritchie, J.C.; Sloan, T.P.; Idle, J.R. and Smith, R.L.: Toxicological implications of polymorphic drug metabolism; in Environmental Chemicals, Enzyme Function and Human Disease (Ciba Foundation Symposium 76), pp.219–244 (Excerpta Medica, Amsterdam 1980).

  • Roe, D.A.: Interactions between drugs and nutrients. Medical Clinics of North America 63: 985–1007 (1979).

    PubMed  CAS  Google Scholar 

  • Schaefer, J.M.: Alcohol metabolism and sensitivity reactions among the Reddis of South India. Alcoholism: Clinical and Experimental Research 2: 61–69 (1978).

    Article  CAS  Google Scholar 

  • Schaefer, J.M.: Ethnic differences in response to alcohol; in Pickens and Heston (Eds) Psychiatric Factors in Drug Abuse, pp. 219–238 (Grune and Stratum, New York 1979).

    Google Scholar 

  • Schull, W.J.: Genetic structure of human populations. Journal of Environmental Pathology and Toxicology 2: 1305–1312 (1979).

    PubMed  CAS  Google Scholar 

  • Scott E.M. and Wright, R.C.: A third type of serum Cholinesterase deficiency in Eskimos. American Journal of Human Genetics 28: 253–256 (1976).

    PubMed  CAS  Google Scholar 

  • Scheiner, L.B. and Beal S.L.: Analysis of nonexperimental pharmacokinetic data; in Albert (Ed.) Drug Absorption and Disposition: Statistical Considerations, pp. 31–49 (American Pharmaceutical Association Academy of Pharmaceutical Sciences, Washington 1980).

    Google Scholar 

  • Sheiner, L.B. and Beal, S.L.: Estimation of pooled pharmacokinetic parameters describing populations; in Endrenyi (Ed.) Kinetic Data Analysis, pp. 271–284 (Plenum Press, New York 1981).

    Chapter  Google Scholar 

  • Sitar, S.D. and Mannering, G.J.: Determination of apparent kinetic constants of the microsomal hydroxylation of amobarbital, hexobarbital, and pentobarbital. Drug Metabolism and Disposition 1: 663–668 (1973).

    PubMed  CAS  Google Scholar 

  • Sloan, T.P.; Idle, J.R. and Smith, R.L.: Influence of DH/DL alleles regulating debrisoquine oxidation on Phenytoin hydroxylation. Clinical Pharmacology and Therapeutics 29: 493–497 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Sloan, T.P.; Mahgoub, A.; Lancaster, R.; Idle, J.R. and Smith R.L.: Polymorphism of carbon oxidation of drugs and clinical implications. British Medical Journal 2: 655–657 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Smith, M.; Hopkinson, D.A. and Harris, H.: Developmental changes and polymorphism in human alcohol dehydrogenase. Annals of Human Genetics (London) 34: 251–271 (1971).

    Article  CAS  Google Scholar 

  • Smith, R.L.: Some clinical and toxicological implications of polymorphic drug oxidation. Communication at Workshop ‘Polymorphism of Drug Oxidation in Man’, University of Bonn (October, 1980).

  • Spector, R.; Choudhury, A.K.; Chiang, C.-K.; Goldberg, M.J. and Ghoneim, M.M: Diphenhydramine in Orientals and Caucasians. Clinical Pharmacology and Therapeutics 28: 229–234 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Srivastava, L.M.; Benkmann, H.G. and Goedde, H.W.: Review on genetic traits in Europeans, Middle East Orientals and Negroes: Serum proteins. Indian Journal of Physical Anthropology and Human Genetics 3: 85–140 (1977).

    Google Scholar 

  • Stamatoyannopoulos, G.; Chen, S.-H. and Fukui, M.: Liver alcohol dehydrogenase in Japanese: High population frequency of atypical form and its possible role in alcohol sensitivity. American Journal of Human Genetics 27: 789–796 (1975).

    PubMed  CAS  Google Scholar 

  • Steegmüller, H.: On the geographical distribution of pseudoCholinesterase variants. Humangenetik 26: 167–185 (1975).

    PubMed  Google Scholar 

  • Stewart, D.J.; Inaba, T.; Tang, B.K. and Kalow, W.: Hydrolysis of cocaine in human plasma by Cholinesterase. Life Sciences 20: 1557–1564 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Tang, B.K. and Carro-Ciampi, G.: A method for the study of N-glucosidation In vitro — amobarbital-N-glucoside formation in incubations with human liver. Biochemical Pharmacology 29: 2085–2088 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Tang, B.K.; Kalow, W.; Endrenyi, L. and Chan, F.Y.: An assessment of short-cut procedures for studying drug metabolism using amobarbital as model drug. European Journal of Clinical Pharmacology 22: 229–233 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Tang, B.K.; Kalow, W. and Grey, A.A.: Amobarbital metabolism in man: N-Glucoside formation. Research Communications in Chemical Pathology and Pharmacology 21: 45–53 (1978).

    PubMed  CAS  Google Scholar 

  • Tang, B.K.; Kalow, W. and Grey, A.A.: Metabolic fate of phenobarbital in man: N-Glucoside formation. Drug Metabolism and Disposition 7: 315–318 (1979).

    PubMed  CAS  Google Scholar 

  • Teng, Y.-S.; Jehan, S. and Lie-lnjo, L.E.: Human alcohol dehydrogenase ADH2 and ADH1 polymorphisms in ethnic Chinese and Indians of West Malaysia. Human Genetics 53: 87–90 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Testa, B. and Jenner, P.: Drug Metabolism: Chemical and Biochemical Aspects (Marcel Dekker Inc., New York 1976).

    Google Scholar 

  • Timbrell, J.A.; Mitchell, J.R.; Snodgrass, W.R. and Nelson, S.D.: Isoniazid hepatotoxicity: The relationship between covalent binding and metabolism in vivo.. Journal of Pharmacology and Experimental Therapeutics 213: 364–369 (1980).

    PubMed  CAS  Google Scholar 

  • Valentino, R.J.; Lockridge, O.; Eckerson, H.W. and LaDu, B.N.: Prediction of drug sensitivity in individuals with atypical serum Cholinesterase based on in vitro biochemical studies. Biochemical Pharmacology 30: 1643–1649 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Van Boxtel, C.J.; Breimer, D.D. and Danhof, M.: Studies on the different metabolic pathways of antipyrine as a tool in the assessment of the activity of different drug metabolizing enzyme systems in man. British Journal of Pharmacology 68: 121P (1980).

    Google Scholar 

  • Vasko, M.R.; Bell, R.D.; Daly, D.D.; and Pippenger, C.E.: Inheritance of Phenytoin hypometabolism. A kinetic study of one family. Clinical Pharmacology and Therapeutics 27: 96–103 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Vesell, E.S.: Genetic and environmental factors affecting drug disposition in man. Clinical Pharmacology and Therapeutics 22: 659–679 (1977).

    PubMed  CAS  Google Scholar 

  • Vesell, E.S.: The value of antipyrine and aminopyrine as model substrates in assessing drug-metabolizing capacity in man. Trends in Pharmacological Sciences 1 (No. 16) [Dec 1980].

  • Vesell, E.S. and Page, J.G.. Genetic control of drug levels in man: Antipyrine. Science 161: 72–73 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Vestergaard, P. and Leverett, R.: Constancy of urinary Creatinine excretion. Journal of Laboratory and Clinical Medicine 51: 211–218 (1958).

    PubMed  CAS  Google Scholar 

  • Viby-Mogensen, J. and Hanel, H.K.: Prolonged apnoea after suxamethonium. An analysis of the first 225 cases reported to the Danish Cholinesterase Research Unit. Acta Anaesthesiologica Scandinavica 22: 371–380 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Wiholm, B.-E.; Alvan, G.; Bertilsson, L.; Sawe, J. and Sjöqvist, F.: Hydroxylation of debrisoquine in patients with 1acticacidosis after phenformin. Lancet 1: 1098–1099 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Wartburg, J.P. von: Acetaldehyde; in Sandier (Ed.) Psychopharmacology of Alcohol, pp. 137–147 (Raven Press, New York 1980).

    Google Scholar 

  • Wartburg, J.-P. von; Papenberg, J. and Aebi, H.: An atypical human alcohol dehydrogenase. Canadian Journal of Biochemistry 43: 889–898 (1965).

    Article  Google Scholar 

  • Wartburg, J.P. von and Schürch, P.M.: Atypical human liver alcohol dehydrogenase. Annals of the New York Academy of Sciences 151: 936–946 (1968).

    Google Scholar 

  • Weinshilboum, R.M. and Raymond, F.A.: Inheritance of low erythrocyte catechol-0-methyltransferase activity in man. American Journal of Human Genetics 29: 125–135 (1977).

    PubMed  CAS  Google Scholar 

  • Weinshilboum, R.M. and Sladek, S.L.: Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American Journal of Human Genetics 32: 651–662 (1980).

    PubMed  CAS  Google Scholar 

  • Woolhouse, N.M.; Andoh, B.; Mahgoub, A.; Sloan, T.P.; Idle, J.R. and Smith R.L.: Debrisoquine hydroxylation polymorphism among Ghanaians and Caucasians. Clinical Pharmacology and Therapeutics 26: 584–591 (1979).

    PubMed  CAS  Google Scholar 

  • Yang, C.S.: Interactions between cytochrome P-450 and NADPH-cytochrome P-450 reductase in the microsomal membrane; in Ullrich et al. (Eds) Microsomes and Drug Oxidations, pp. 9–16 (Pergamon Press, Oxford 1977).

    Google Scholar 

  • Zeiner, A.R. and Paredes, A.: Racial differences in arcadian variation of ethanol metabolism. Alcoholism: Clinical and Experimental Research 2: 71–75 (1978).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Toronto, Toronto, Ontario, M55 1A8, Canada

    W. Kalow

Authors
  1. W. Kalow
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalow, W. Ethnic Differences in Drug Metabolism. Clin Pharmacokinet 7, 373–400 (1982). https://doi.org/10.2165/00003088-198207050-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198207050-00001

Keywords

Search

Navigation