Interethnic Differences in Drug Disposition and Response: Relevance for Drug Development, Licensing, and Registration

  • L. P. Balant
  • P. G. Welling
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 110)

Abstract

In 1982, Kalow introduced his review on “Ethnic differences in drug metabolism” by stating that: “the literature contains a number of examples of differences between populations in drug metabolizing capacity. Although this topic has been discussed previously as part of pharmacogenetics review, it deserves a new effort with different emphasis on a recently expanded data base. The topic should help improve understanding of human biology, and is of practical significance in pharmacology and toxicology.” Ten years later the same statement is still true and considerable knowledge has been acquired at the molecular biology level. As a matter of fact, a recently published book on pharmacogenetics (Kalow 1992) contains important and extensive information on interethnic differences in drug metabolism. Accordingly, the authors of the present review decided to concentrate their presentation on aspects related essentially to drug development, licensing, and registration in the context of the new “4 W” environment (i.e., What and Why to present for World Wide drug registration). In this framework, pharmacokinetic/ pharmacodynamic (PK/PD) relationships are also becoming of importance, as exemplified by a recent conference (PECK et al. 1992), and the authors felt that their presentation should deal also with some aspects of interethnic differences in drug tolerance and response. However, the wide-ranging subject of interethnic differences in drug response and tolerance will not be discussed in detail in the present review and interested readers are referred to treatises of internal medicine such as the Harrison’s (Braunwald et al. 1988). Nevertheless, PK/PD relationships will serve as a reference framework for this chapter on interethnic differences in drug metabolism.

Keywords

Tuberculosis Caffeine Diazepam Paracetamol Nifedipine 

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References

  1. Allaz AF, Dayer P, Fabre J, Rudhardt M, Balant L (1979) Pharmacocinétique d’une nouvelle céphalosporin, la céfopérazone. Schweiz Med Wochenschr 109: 1999–2005PubMedGoogle Scholar
  2. Alván G, Bechtel P, Iselius L, Gundert-Remy U (1990) Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 39: 533–537PubMedGoogle Scholar
  3. Balant LP, Gorgia A, Tschopp JM, Revillard C, Fabre J (1976) Pharmacocinétique de deux médicaments bêta-bloquants: détection d’une anomalie pharmacogénétique? Schweiz Med Wochenschr 106: 1403–1407PubMedGoogle Scholar
  4. Balant LP, Gundert-Remy U, Boobis AR, von Bahr C (1989) Relevance of genetic polymorphism in drug metabolism in the development of new drugs. Eur J Clin Pharmacol 36: 551–554PubMedGoogle Scholar
  5. Balant LP, Roseboom H, Gundert-Remy U (1990) Pharmacokinetic criteria for drug research and development. Adv Drug Res 19: 1–139Google Scholar
  6. Bertilsson L (1990) Interethnic differences in drug oxidation polymorphism. In: Alvan G, Balant LP, Bechtel PR, Boobis AR, Gram LF, Pithan K (eds) European consensus conference on pharmacogenetics. Commission of the European Communities, Luxembourg, pp 171–178 (Coordinated action COST B1 )Google Scholar
  7. Bertilsson L, Henthorn TK, Sanz E, Tybring G, Säwe J, Villén T (1989) Importance of genetic factors in the regulation of diazepam metabolism: relationship to Smephenytoin, but not debrisoquine, hydroxylation phenotype. Clin Pharmacol Ther 45: 348–355PubMedGoogle Scholar
  8. Braunwald E et al. (eds) (1988) Harrison’s principles of internal medicine, 11th edn. McGraw-Hill, New YorkGoogle Scholar
  9. Darmansjah I, Muchtar A (1992) Dose-response variation among different populations. Clin Pharmacol Ther 52: 449–452PubMedGoogle Scholar
  10. Dayer P, Balant LP, Courvoisier F, Küpfer A, Kubli A, Gorgia A, Fabre J (1982) The genetic control of bufuralol metabolism in man. Eur J Drug Metab Pharmacokinet 7: 73–77PubMedGoogle Scholar
  11. Dayer P, Balant LP, Kiipfer, A, Courvoisier F, Fabre J (1983) Contribution of the genetic status of oxidative metabolism to variability in the plasma concentrations of beta-adrenoceptor blocking agents. Eur J Clin Pharmacol 24: 797–799PubMedGoogle Scholar
  12. Dayer P, Balant LP, Küpfer A, Striberni R, Leemann T (1985) Effect of oxidative polymorphism (debrisoquine/sparteine type) on hepatic first-pass metabolism of bufuralol. Eur J Clin Pharmacol 28: 317–320PubMedGoogle Scholar
  13. Ebelin ME, Steimer JL, Laplanche R, Niederberger W (1992) An evaluation of population pharmacokinetics during drug development: experiences with graphical exploratory analysis for isradipine and tropisetron. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 131–141 (Coordinated action COST B1 )Google Scholar
  14. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective Noxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16: 183–187PubMedGoogle Scholar
  15. Evans DAP (1992) N-acetyltransferase. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon, New York, pp 95–178Google Scholar
  16. Ghoneim MM, Korttila K, Chiang CK, Jacobs L, Schoenwald RD, Mewaldt SP, Kabaya KO (1981) Diazepam effects and kinetics in Caucasians and Orientals. Clin Pharmacol Ther 29: 749–756PubMedGoogle Scholar
  17. Gundert-Remy U (1992) Population approach in pharmacokinetic and pharmacodynamics—views within regulatory agencies: Europe. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 153–156 (Coordinated action COST B1 )Google Scholar
  18. Hermansson J, von Bahr C (1982) Determination of (R)- and (S)-alprenolol and (R)- and (S)-metoprolol diastereoisomeric derivatives in human plasma by reversedphase liquid chromatography. J Chromatogr 227: 113–127PubMedGoogle Scholar
  19. Holford NHG (1992) Parametric models for the time course of drug action: the population approach. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 193–206 (Coordinated action COST B1 )Google Scholar
  20. Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou HH, Zhou BJ, Lia CL, Zhang LM (1989) Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese. Clin Pharmacol Ther 46: 198–207PubMedGoogle Scholar
  21. Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ (1987) Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol 23: 482–485PubMedGoogle Scholar
  22. Joubert PH, Brandt HD (1990) Apparent racial difference in response to angiotensin I infusion. Eur J Clin Pharmacol 39: 183–185PubMedGoogle Scholar
  23. Kalow W (1982) Ethnic differences in drug metabolism. Clin Pharmacokinet 7: 373–400PubMedGoogle Scholar
  24. Kalow W (1984) Pharmacoanthropology: outline, problems, and the nature of case histories. Fed Proc 43: 2314–2318PubMedGoogle Scholar
  25. Kalow W (1992) Pharmacoanthropology and the genetics of drug metabolism. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon, New York, pp 865–877Google Scholar
  26. Katz MM, Katz MM, Kato M, Yamamoto J et al. (1979) Transcultural psychopharmacology in depression: East and West. Psychopharmacol Bull 15: 24–31Google Scholar
  27. Kubli A, Balant LP, Dayer P, Balant-Gorgia A, Fabre J (1982) Influence du polymorphisme génétique de l’oxydation sur les études de biodisponibilité: a propos du bufuralol. J Pharmacol Clin 1: 301–315Google Scholar
  28. Kumana CR, Lauder IJ, Chan M, Ko W, Lin HJ (1987) Differences in diazepam pharmacokinetics in Chinese and white Caucasians—relation to body lipid stores. Eur J Clin Pharmacol 32: 211–215PubMedGoogle Scholar
  29. Küpfer A, Preisig R (1984) Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol 26: 753–759PubMedGoogle Scholar
  30. Lennard MS (1992) The polymorphic oxidation of beta-adrenoceptor antagonists. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon, New York, pp 701–720Google Scholar
  31. Lennard MS, Tucker GT, Silas JH, Freestone S, Ramsay LW, Woods HF (1983) Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquine metabolisers. Clin Pharmacol Ther 34: 732–737PubMedGoogle Scholar
  32. Lou YC, Ying L, Bertilsson L, Sjoqvist F (1987) Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet 2: 852–853PubMedGoogle Scholar
  33. Mahgoub A, Idle JR, Dring LG, Lancester R, Smith RL (1977) Polymorphic hydroxylation of debrisoquine in man. Lancet 2: 584–586PubMedGoogle Scholar
  34. Mendoza R, Smith MW, Poland RE, Lin KM, Strickland TL (1991) Ethnic psychopharmacology: the Hispanic and native American perspective. Psychopharmacol Bull 27: 449–461PubMedGoogle Scholar
  35. Meyer UA, Zanger UM, Grant D, Blum M (1990) Genetic polymorphisms of drug metabolism. Adv Drug Res 19: 197–241Google Scholar
  36. Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA (1985) Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 38: 402–408PubMedGoogle Scholar
  37. Peck CC (1992) Population approach in pharmacokinetics and pharmacodynamics: FDA view. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 157–168 (Coordinated action COST B1 )Google Scholar
  38. Peck CC, Barr WH, Benet LZ, et al. (1992) Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development. Clin Pharmacol Ther 51: 465–473PubMedGoogle Scholar
  39. Sheiner LB (1992) Population approach in drug development: rationale and basic concepts. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 13–27 (Coordinated action COST B1 )Google Scholar
  40. Strickland TL, Ranganath V, Lin KM, Poland RE, Mendoza R, Smith MW (1991) Psychopharmacologic considerations in the treatment of black American populations. Psychopharmacol Bull 27: 441–448PubMedGoogle Scholar
  41. Vozeh S (1992) Applications of population approach to clinical pharmacokinetics and validation of results. In: Rowland M, Aarons L (eds) New strategies in drug development and clinical evaluation: the population approach. Commission of the European Communities, Luxembourg, pp 107–120 (Coordinated action COST B1 )Google Scholar
  42. Yue QY, Bertilsson L, Dahl-Puustinen ML, Sawe J, Sjoqvist F, Johansson I, Ingelman-Sundberg M (1989) Dissociation between debrisoquine hydroxylation phenotype and genotype among Chinese. Lancet 2: 870PubMedGoogle Scholar
  43. Zhou HH, Wood AJJ (1990) Differences in stereoselective disposition of propranolol do not explain sensitivity differences between white and Chinese subjects: correlation between the clearance of (-)—and (+)-propranolol. Clin Pharmacol Ther 47: 719–723PubMedGoogle Scholar

I. Phenotypes of N-acetylation

  1. Afonia AO, Arharwarien ED, Okotore RO, Femi-Pearse D (1979) Isoniazid acetylator phenotypes of Nigerians. Nigerian Med J 9: 86–88Google Scholar
  2. Airaksinen E, Mattila MJ, Olilla O (1969) Inactivation of isoniazid and sulphadimidine in Mongoloid subjects. Ann Med Exp Biol Fenn 47: 303–307PubMedGoogle Scholar
  3. Armstrong AR, Peart HE (1960) A comparison between the behaviour of Eskimos and non-Eskimos to the administration of isoniazid. Am Rev Respir Dis 81: 588–594PubMedGoogle Scholar
  4. Bouayad Z, Chevalier B, Maurin R, Bartal M (1982) Phénotype d’acétylation de l’isoniazide au Maroc. Etude preliminaire sur 100 cas. Rev Maroc Med Sante 4: 13–18Google Scholar
  5. Bozkurt A, Basci NE, Tuncer M, Kayaalp SO (1990) N-acetylation phenotyping with sulphadimidine in a Turkish population. Eur J Clin Pharmacol 38: 53–56PubMedGoogle Scholar
  6. Bressolette L, Berthou F, Riche C, Mottier D, Floch HH (1990) Polymorphisme genetique d’acetylation et d’hydroxylation dans la population bretonne. Thérapie 45: 99–103Google Scholar
  7. Desai M, Jariwala G, Khokhani B, Desai NK, Sheth UK (1973) Isoniazid inactivation in Indian children. Indian Pediatr 10: 373–376PubMedGoogle Scholar
  8. Eidus L, Hodgkin MM, Schaeffer O, Jessamine AG (1974) Distribution of isoniazid inactivators determined in Eskimos and Canadian college students by a urine test. Rev Can Biol 33: 117–123PubMedGoogle Scholar
  9. Eidus L, Glatthaar E, Hodgkin MM, Nel EE, Kleeberg HH (1979) Comparison of isoniazid phenotyping of black and white patients with emphasis on South African blacks. Int J Clin Pharmac Biopharm 17: 311–316Google Scholar
  10. El-Yazigi A, Chaleby K, Martin CR (1989) Acetylator phenotypes of Saudi Arabians by a simplified caffeine metabolite test. J Clin Pharmacol 29: 246–250PubMedGoogle Scholar
  11. Evans DAP, Paterson S, Francisco P, Alvarez G (1985) The acetylator phenotype of Saudi Arabian diabetics. J Med Genet 22: 479–483PubMedGoogle Scholar
  12. Evans DAP, Wicks J, Higgins J, Assisto M (1991) The acetylator phenotypes of Saudi Arabians with coronary arterial atheroma. J Med Genet 28: 192–193PubMedGoogle Scholar
  13. Eze LC (1987) High incidence of the slow nitrazepam acetylator phenotype in a Nigerian population. Biochem Genet 25: 225–229PubMedGoogle Scholar
  14. Eze LC, Obidoa O (1978) The acetylation of sulphamethazine in a Nigerian population. Biochem Genet 16: 1073–1077PubMedGoogle Scholar
  15. Fawcett IW, Gammon PT (1975) Determination of the acetylator phenotype in a Northern Nigerian population. Tubercle 56: 119–201Google Scholar
  16. Goedde HW, Benkmann HG, Agarwal DP, Kroeger A (1977a) Genetic studies in Ecuador; acetylator phenotypes, red cell enzyme and serum protein polymorphisms of Shuara indians. Am J Phys Anthropol 47: 419–425PubMedGoogle Scholar
  17. Goedde HW, Flatz G, Rahimi AG, Kaifie S, Benkmann HG, Kreise G, Delbriick H (1977b) The acetylator polymorphism in four populations of Afghanistan. Hum Hered 27: 383–388PubMedGoogle Scholar
  18. Gupta RC, Nair CR, Jindal SK, Malik SK (1984) Incidence of isoniazid acetylation phenotypes in North Indians. Int Clin Pharmacol Ther Toxicol 22: 259–264Google Scholar
  19. Gurumurthy P, Krisnamurthy MS, Nazareth O, Parthasarathy R, Raghupati Sarma G, Somasundaram PR, Tripathy SP, Ellard GA (1984) Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis. Am Rev Respir Dis 129: 58–61PubMedGoogle Scholar
  20. Hayward GA (1975) Human acetylation polymorphism in Polynesians. Proc Univ Otago Med Sch 53: 67–68Google Scholar
  21. Hilderbrand M, Seifert W (1989) Determination of acetylator phenotype in Caucasians with caffeine. Eur J Clin Pharmacol 37: 525–526Google Scholar
  22. Homeida M, Abboud OI, Dawi O, Rahama AM, Awad EH, Ahmed OM (1986) The acetylator phenotype of Sudanese subjects. Arab J Med 5: 30–31Google Scholar
  23. Horai Y, Ishizaki T (1988) N-acetylation polymorphism of dapsone in a Japanese population. Br J Clin Pharmacol 25: 487–494PubMedGoogle Scholar
  24. Horai Y, Ishizaki T, Sasaki T, Koya G, Matsuyama K, Iguelin S (1982) Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic lupus erythematosus and control subjects. Br J Clin Pharmacol 13: 361–374PubMedGoogle Scholar
  25. Horai Y, Zhou HH, Zhang LM, Ishizaki T (1988) Acetylation phenotyping with dapsone in a mainland Chinese population. Br J Clin Pharmacol 25: 81–87PubMedGoogle Scholar
  26. Horai Y, Fujita K, Ishizaki T (1989) Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer. Eur J Clin Pharmacol 37: 581–587PubMedGoogle Scholar
  27. Inaba T, Arias TD (1987) On phenotyping with isoniazid. The use of urinary acetylation/ratios and the uniqueness of antimodes found in two Amerindian populations. Clin Pharmacol Ther 42: 493–497PubMedGoogle Scholar
  28. Irshaid YM, Al-Halidi HF, Abuirjeie MA, Rawasheh NM (1991) N-acetylation phenotyping using dapsone in a Jordanian population. Br J Clin Pharmacol 32: 1039–1057Google Scholar
  29. Irshaid YM, Al-Hadidi HF, Abuirjeie MA, Latif A, Sartawi O, Rawashed NM (1992) Acelylator phenotype of Jordanian diabetics. Eur J Clin Pharmacol 43: 621–623PubMedGoogle Scholar
  30. Islam SI (1982) Polymorphic acetylation of sulphamethyzine in rural Bedouin and urban-dwellers in Saudi Arabia. Xenobiotica 12: 323–328PubMedGoogle Scholar
  31. Jenkins T, Lehmann H, Nurse GP (1974) Public health and genetic constitution of the Sab (“Bushmen”): carbohydrate metabolism and acetylator status of the Kung of Tsumkwe in the North-Western Kalahari. Br Med J 2: 23–26PubMedGoogle Scholar
  32. Karim AKMB, Elfellah MS, Evans DAP (1981) Human acetylator polymorphism: estimate of allele frequency in Libya and details of global distribution. J Med Genet 18: 325–330PubMedGoogle Scholar
  33. Lee EJD, Lim JME, Feng P-H (1985) Acetylator phenotype in Chinese patients with spontaneous systemic lupus erythematosus. Syngapore Med J 26: 295–299Google Scholar
  34. Lilyin ET, Korunskaya MP, Meksin VA, Taelicheva LV, Shapiro EF (1983) The distribution of acetylator phenotypes in Moscow population. Genetika 19: 1378–1380Google Scholar
  35. Lilyin ET, Korunskaya MP, Meksin VA, Drozdov ES, Nasarov VV, Monastyrskaya AR (1984) The distribution of acetylator phenotypes in normal individuals and the patients suffering from alcoholism among Moscow urban population. Genetika 20: 1557–1559Google Scholar
  36. Lower GM Jr, Nilsson T, Nelson CE, Wolf H, Gamsky TE, Bryan GT (1979) Nacetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark. Environ Health Perspect 29: 71–79PubMedGoogle Scholar
  37. Nhachi CFB (1988) Polymorphic acetylation of sulphamethazine in a Zimbabwe population. J Med Genet 25: 29–31PubMedGoogle Scholar
  38. Odeigah PGC, Okunowo MA (1989) High frequency of the rapid isoniazid acetylator phenotype in Lagos ( Nigeria ). Hum Hered 39: 26–31PubMedGoogle Scholar
  39. Paik YK, Cho YH, Kim IK, Benkmann HG, Goedde HW (1988) Pharmacogenetic studies in South Korea: serum cholinesterase and N-acetyltransferase polymorphisms. Korean J Genet 10: 272–278Google Scholar
  40. Parthasarathy R, Raghupati Sarma G, Janardhanam B, Ramachandran P, Santha T, Sivasubramaian S, Somasundaram PR, Tripathy SP (1986) Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle 67: 99–108PubMedGoogle Scholar
  41. Paulsen O, Nilsson LG (1985) Distribution of acetylator phenotype in relation to age and sex in Swedish patients. Eur J Clin Pharmacol 28: 311–315PubMedGoogle Scholar
  42. Penketh RJA, Gibreig SFA, Nurse GT, Hopkinson DA (1983) Acetylator phenotypes in Papua New Guinea. J Med Genet 20: 39–40Google Scholar
  43. Peters JH, Gordon GT, Karat ABA (1975) Polymorphic acetylation of the antibacterials, sulfamethazine and dapsone, in South Indian subjects. Am J Trop Med Hyg 24: 641–648PubMedGoogle Scholar
  44. Sardas S, Karakaya AE, Cok I (1986a) Determination of the acetylator phenotype in a Turkish population. Clin Genet 29: 185–186PubMedGoogle Scholar
  45. Tang BK, Kadar D, Qian L, Iriah J, Yip J, Kalow W (1991) Caffeine as a metabolic probe: validation of its use for acetylator phenotyping ( Various ethnic groups ). Clin Pharmacol Ther 49: 648–657PubMedGoogle Scholar
  46. Viznerova A, Slavikova Z, Ellard GA (1973) The determination of the acetylator phenotype of tuberculosis patients in Czechoslovakia using sulphadimidine. Tubercle 54: 67–76PubMedGoogle Scholar

II. Phenotypes of Hydroxylation

  1. Alvan G, Bechtel P, Iselius L, Gundert-Remy U (1990) Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 39: 533–537PubMedGoogle Scholar
  2. Arias TD, Jorge LF, Inaba T (1986) No evidence for the presence of poor metabolizers of sparteine in an Amerindian group: the Cunas of Panama. Br J Clin Pharmacol 21: 547–548PubMedGoogle Scholar
  3. Arias TD, Jorge LF, Lee D, Barrantes R, Inaba T (1988a) The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers. Clin Pharmacol Ther 43: 456–465PubMedGoogle Scholar
  4. Arias TD, Inaba T, Cooke RG, Jorge LF (1988b) A preliminary note on the transient polymorphic oxidation of sparteine in the Ngawbé Guaymi Amerindians: a case of genetic divergence with tentative phylogenetic time frame for the pathway. Clin Pharmacol Ther 44: 343–352PubMedGoogle Scholar
  5. Arvela P, Kirjarinta M, Kirjarinta M, Karki N, Pelkonen O (1988) Polymorphism of debrisoquine hydroxylation among Finns and Lapps. Br J Clin Pharmacol 26: 601–603PubMedGoogle Scholar
  6. Benitez J, Llerena A, Cobaleda (1988) Debrisoquin oxidation polymorphism in a Spanish population. Clin Pharmacol Ther 44: 74–77PubMedGoogle Scholar
  7. Bressolette L, Berthou F, Riche C, Mottier D, Floch HH (1990) Polymorphisme génétique d’acetylation et d’hydroxylation dans la population bretonne. Therapie 45: 99–103Google Scholar
  8. Brøsen K (1986) Sparteine oxidation polymorphism in Greenlanders living in Denmark. Br J Clin Pharmacol 22: 415–419PubMedGoogle Scholar
  9. Brøsen K, Otton SV, Gram LF (1985) Sparteine oxidation polymorphism in Denmark. Acta Pharmacol Toxicol (Copenh) 57: 357–360Google Scholar
  10. Clasen K, Madsen L, Brøsen K, Albøge K, Misfeldt S, Gram LF (1991) Sparteine and mephenytoin oxidation: genetic polymorphisms in East and West Greenland. Clin Pharmacol Ther 49: 624–631PubMedGoogle Scholar
  11. Dayer P, Balant LP, Courvoisier F, Küpfer A, Kubli A, Gorgia A, Fabre J (1982) The genetic control of bufuralol metabolism in man ( Switzerland ). Eur J Drug Metab Pharmacokinet 7: 73–77PubMedGoogle Scholar
  12. Dayer P, Balant L, Küpfer A, Courvoisier F, Fabre J (1983) Contribution of the genetic status of oxidative metabolism to variability in the plasma concentrations of beta-adrenoceptor blocking agents (bufuralol in Switzerland). Eur J Clin Pharmacol 24: 797–799PubMedGoogle Scholar
  13. Dick B, Küpfer A, Molnàr J, Braunschweig S, Preisig R (1982) Hydroxylierungsdefekt für Medikamente ( Typus Debrisoquin) in einer Stichprobe der Schweizerischen Bevölkerung. Schweiz Med Wochenschr 112: 1061–1067PubMedGoogle Scholar
  14. Drøhse A, Bathum L, Brøsen K, Gram LF (1989) Mephenytoin and sparteine oxidation: genetic polymorphism in Denmark. Br J Clin Pharmacol 27: 620–625PubMedGoogle Scholar
  15. Eichelbaum M, Woolhouse NM (1985) Inter-ethnic difference in sparteine oxidation among Ghanaians and Germans. Eur J Clin Pharmacol 28: 79–83PubMedGoogle Scholar
  16. Evans DAP, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980) A family and population study of the genetic polymorphism of debrisoquine oxidative in a white British population. Br J Med Genet 17: 102–105Google Scholar
  17. Horai Y, Ishizaki T, Ishikawa K (1988) Metoprolol oxidation in a Japanese population: evidence for only one poor metabolizer among 262 subjects. Br J Clin Pharmacol 26: 807–808PubMedGoogle Scholar
  18. Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou HH, Zhou BJ, Lia CL, Zhang LM (1989) Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese. Clin Pharmacol Ther 46: 198–207PubMedGoogle Scholar
  19. Inaba T, Jurima M, Nakano M, Kalow W (1984) Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians. Clin Pharmacol Ther 36: 670–676PubMedGoogle Scholar
  20. Inaba T, Jorge LF, Arias TD (1988) Mephenytoin hydroxylation in the Cuna Amerindians of Panama. Br J Clin Pharmacol 25: 75–79PubMedGoogle Scholar
  21. Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ (1987) Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol 23: 482–485PubMedGoogle Scholar
  22. Islam SI, Idle JR, Smith RL (1980) The polymorphic 4-hydroxylation of debrisoquin in a Saudi Arab population. Xenobiotica 10: 819–825PubMedGoogle Scholar
  23. Iyun AO, Lennard MS, Tucker GT, Woods HF (1986) Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation. Clin Pharmacol Ther 40: 387–394PubMedGoogle Scholar
  24. Jacqz E, Dulac H, Mathieu H (1988) Phenotyping polymorphic drug metabolism in the French Caucasian population. Eur J Clin Pharmacol 35: 167–171PubMedGoogle Scholar
  25. Jurima M, Inaba T, Kadar D, Kalow W (1985) Genetic polymorphism of mephenytoin p(41)-hydroxylation: difference between Orientals and Caucasians. Br J Clin Pharmacol 19: 483–487PubMedGoogle Scholar
  26. Kallio J, Lindberg R, Huuponen R, lisalo E (1988) Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio. Br J Clin Pharmacol 26: 791–795PubMedGoogle Scholar
  27. Kalow W, Otton SV, Kadar D, Endrenyi L, Inaba T (1980) Ethnic differences in drug metabolism: debrisoquine 4-hydroxylation in Caucasians and Orientals. Can J Physiol Pharmacol 58: 1142–1144PubMedGoogle Scholar
  28. Küpfer A, Preisig R (1984) Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man ( Switzerland ). Eur J Clin Pharmacol 26: 753–759PubMedGoogle Scholar
  29. Larrey D, Amouyal G, Tinel M, Letteron P, Berson A, Labbe G, Pessayre D (1987) Polymorphism of dextromethorphan oxidation in a French population. Br J Clin Pharmacol 24: 676–679PubMedGoogle Scholar
  30. Leclercq V, Desager JP, van Nieuwenhuyze Y, Harvengt C (1987) Prevalence of drug hydroxylator phenotype in Belgium. Eur J Clin Pharmacol 33: 439–440PubMedGoogle Scholar
  31. Lennard MS, Tucker GT, Woods HF, Silas JH, Iyun AO (1989) Stereoselective metabolism of metoprolol in Caucasians and Nigerians—relationship to debrisoquin oxidation phenotype. Br J Clin Pharmacol 27: 613–616PubMedGoogle Scholar
  32. Lou YC, Ying L, Bertilsson L, Sjöqvist F (1987) Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet 2: 852–853PubMedGoogle Scholar
  33. Mahgoub A, Idle JR, Smith RL (1979) A population and familial study of the defective alicyclic hydroxylation of debrisoquine among Egyptians. Xenobiotica 9: 51–56PubMedGoogle Scholar
  34. Mbanefo C, Bababunmi EA, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980) A study of the debrisoquine hydroxylation polymorphism in a Nigerian population. Xenobiotica 10: 811–818PubMedGoogle Scholar
  35. Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA (1985) Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 38: 402–408PubMedGoogle Scholar
  36. Peart GF, Boutagy J, Shenfield GM (1986) Debrisoquine oxidation in an Australian population. Br J Clin Pharmacol 21: 465–471PubMedGoogle Scholar
  37. Relling MV, Cherries J, Schell MJ, Petros WP, Meyer WH, Evans WE (1991) Lower prevalence of the debrisoquin oxidative poor metabolizer phenotype in American black versus white subjects. Clin Pharmacol Ther 50: 308–313PubMedGoogle Scholar
  38. Schellens JHM, Danhof M, Breimer DD (1986) The poor metabolizer incidence of sparteine, mephenytoin and nifedipine in a Dutch population. Acta Pharmacol Toxicol (Copenh) Suppl 5: 252Google Scholar
  39. Steiner E, Bertilsson L, Sawe J, Bertling I, Sjoqvist F (1988) Polymorphic debrisoquine hydroxylation in 757 Swedish subjects. Clin Pharmacol Ther 44: 431–435PubMedGoogle Scholar
  40. Sommers DK, Moncrieff J, Avenant J (1989) Metoprolol a-hydroxylation polymorphism in the San Bushmen of Southern Africa. Hum Toxicol 8: 39–43PubMedGoogle Scholar
  41. Sommers DK, Moncrieff J, Avenant J (1989) Non-correlation between debrisoquine and metoprolol polymorphisms in the Venda. Hum Toxicol 8: 365–368PubMedGoogle Scholar
  42. Szórády I, Sánta A (1987) Drug hydroxylator phenotype in Hungary. Eur J Clin Pharmacol 32: 325PubMedGoogle Scholar
  43. Veronese ME, McLean S (1991) Debrisoquine oxidation polymorphism in a Tasmanian population. Eur J Clin Pharmacol 40: 529–532PubMedGoogle Scholar
  44. Vinks A, Inaba T, Otton SV, Kalow W (1982) Sparteine metabolism in Canadian Caucasians. Clin Pharmacol Ther 31: 23–29PubMedGoogle Scholar
  45. Wedlund PJ, Aslanian WS, McAllister CB, Wilkinson GR, Branch RA (1984) Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin Pharmacol Ther 36: 773–780PubMedGoogle Scholar
  46. Woolhouse NM, Andoh B, Mahgoub A, Sloan TP, Idle JR, Smith RL (1979) Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther 26: 584–591PubMedGoogle Scholar
  47. Woolhouse NM, Eichelbaum, Oates NS, Idle JR, Smith RL (1985) Dissociation of co-regulatory control of debrisoquin/phenformin and sparteine oxidation in Ghanaians. Clin Pharmacol Ther 37: 512–521PubMedGoogle Scholar
  48. Yue QY, Bertilsson L, Dahl-Puustinen ML, Sawe J, Sjoqvist F, Johansson I, Ingelman-Sundberg M (1989) Dissociation between debrisoquine hydroxylation phenotype and genotype among Chinese. Lancet 2: 870PubMedGoogle Scholar

III. Pharmacokinetics

  1. Branch RA, Salih SY, Homeida M (1978) Racial differences in drug metabolizing ability: a study with antipyrine in the Sudan. Clin Pharmacol Ther 24: 283–286PubMedGoogle Scholar
  2. Buchanan N, Bill P, Moodley G, Eyberg C (1977) The metabolism of phenobarbitone in black patients. S Afr Med J 52: 394–395PubMedGoogle Scholar
  3. Desai NK, Sheth UK, Mucklow JC, Fraser HS, Bulpitt CJ, Jones SW, Dollery CT (1980) Antipyrine clearance in Indian villagers. Br J Clin Pharmacol 9: 387–394PubMedGoogle Scholar
  4. Chan E, Ti TY, Lee HS (1990) Population pharmacokinetics of phenytoin in Singapore Chinese. Eur J Clin Pharmacol 39: 177–181PubMedGoogle Scholar
  5. De Sommers K, Van Staden DA, Moncrieff J, Schoenman HS (1985) Paracetamol metabolism in African villagers. Hum Toxicol 4: 385–389PubMedGoogle Scholar
  6. De Sommers K, Moncrieff J, Avenant JC (1987) Paracetamol conjugation: an interethnic and dietary study. Hum Toxicol 6: 407–409PubMedGoogle Scholar
  7. Ghoneim MM, Korttila K, Chiang CK, Jacobs L, Schoenwald RD, Mewaldt SP, Kabaya KO (1981) Diazepam effects and kinetics in Caucasians and Orientals. Clin Pharmacol Ther 29: 749–756PubMedGoogle Scholar
  8. Kalow W, Tang BK, Kadar D, Endrenyi L, Chan FY (1979) A method for studying drug metabolism in populations: racial differences in amobarbital metabolism. Clin Pharmacol Ther 26: 766–776PubMedGoogle Scholar
  9. Kromann N, Christiansen J, Flachs H, Dam M, Hvidberg EF (1981) Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes. Ther Drug Monit 3: 239–245PubMedGoogle Scholar
  10. Kumana CR, Lauder IJ, Chan M, Ko W, Lin HJ (1987) Differences in diazepam pharmacokinetics in Chinese and white Caucasians—relation to body lipid stores. Eur J Clin Pharmacol 32: 211–215PubMedGoogle Scholar
  11. Pi EH, Tran-Johnson TK, Walker NR, Cooper TB, Suckow RF, Gray GE (1989) Pharmacokinetics of desipramine in Asian and Caucasian volunteers. Psychopharmacol Bull 25: 483–487PubMedGoogle Scholar
  12. Rudorfer MV, Lane EA, Chang WH, Zhang M, Potter WZ (1984) Desipramine pharmacokinetics in Chinese and Caucasian volunteers. Br J Clin Pharmacol 17: 433–440PubMedGoogle Scholar
  13. Spector R, Choudhury AK, Chiang CK, Goldberg MJ, Ghoneim MM (1980) Diphenhydramine in Orientals and Caucasians. Clin Pharmacol Ther 28: 229–234PubMedGoogle Scholar
  14. Zhou HH, Wood AJJ (1990) Differences in stereoselective disposition of propranolol do not explain sensitivity differences between white and Chinese subjects: correlation between the clearance of (-)-and (+)-propranolol. Clin Pharmacol Ther 47: 719–723PubMedGoogle Scholar
  15. Zhou HH, Adedoyin A, Wilkinson GR (1990) Differences in plasma binding of drugs between Caucasians and Chinese subjects. Clin Pharmacol Ther 48: 10–17PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • L. P. Balant
  • P. G. Welling

There are no affiliations available

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