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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1985 Apr;19(4):483–487. doi: 10.1111/j.1365-2125.1985.tb02673.x

Genetic polymorphism of mephenytoin p(4')-hydroxylation: difference between Orientals and Caucasians.

M Jurima, T Inaba, D Kadar, W Kalow
PMCID: PMC1463809  PMID: 3994895

Abstract

The genetically controlled mephenytoin p(4')-hydroxylation capacity was determined in 118 Caucasians and 70 Orientals. After an oral dose of 50 or 100 mg of racemic mephenytoin, the amount of p(4')-hydroxymephenytoin in 24 h urine was measured by gas chromatography. Bimodal distribution was found with 9/70 (13%) Orientals and 5/118 (4%) Caucasians demonstrating deficient p(4')-hydroxylation. The statistically significant difference between Orientals and Caucasians (P less than 0.05) was accounted for by the high incidence of poor metabolizers among the Japanese subjects, 7/31 (23%). The frequency among Chinese subjects, 2/39 (5%), was similar to the frequency among Caucasians.

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Selected References

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  1. Boobis A. R., Murray S., Kahn G. C., Robertz G. M., Davies D. S. Substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man. Mol Pharmacol. 1983 Mar;23(2):474–481. [PubMed] [Google Scholar]
  2. Ellard G. A. Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin Pharmacol Ther. 1976 May;19(5 Pt 2):610–625. doi: 10.1002/cpt1976195part2610. [DOI] [PubMed] [Google Scholar]
  3. Grant D. M., Tang B. K., Kalow W. Variability in caffeine metabolism. Clin Pharmacol Ther. 1983 May;33(5):591–602. doi: 10.1038/clpt.1983.80. [DOI] [PubMed] [Google Scholar]
  4. Harada S., Agarwal D. P., Goedde H. W. Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing. Hum Genet. 1978 Jan 19;40(2):215–220. doi: 10.1007/BF00272304. [DOI] [PubMed] [Google Scholar]
  5. Harada S., Misawa S., Agarwal D. P., Goedde H. W. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. Am J Hum Genet. 1980 Jan;32(1):8–15. [PMC free article] [PubMed] [Google Scholar]
  6. Inaba T., Jurima M., Nakano M., Kalow W. Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians. Clin Pharmacol Ther. 1984 Nov;36(5):670–676. doi: 10.1038/clpt.1984.238. [DOI] [PubMed] [Google Scholar]
  7. Inaba T., Nakano M., Otton S. V., Mahon W. A., Kalow W. A human cytochrome P-450 characterized by inhibition studies as the sparteine-debrisoquine monooxygenase. Can J Physiol Pharmacol. 1984 Jul;62(7):860–862. doi: 10.1139/y84-144. [DOI] [PubMed] [Google Scholar]
  8. Jurima M., Inaba T., Kalow W. Sparteine oxidation by the human liver: absence of inhibition by mephenytoin. Clin Pharmacol Ther. 1984 Mar;35(3):426–428. doi: 10.1038/clpt.1984.54. [DOI] [PubMed] [Google Scholar]
  9. Kalow W., Otton S. V., Kadar D., Endrenyi L., Inaba T. Ethnic difference in drug metabolism: debrisoquine 4-hydroxylation in Caucasians and Orientals. Can J Physiol Pharmacol. 1980 Sep;58(9):1142–1144. doi: 10.1139/y80-173. [DOI] [PubMed] [Google Scholar]
  10. Kalow W., Tang B. K., Kadar D., Endrenyi L., Chan F. Y. A method for studying drug metabolism in populations: racial differences in amobarbital metabolism. Clin Pharmacol Ther. 1979 Dec;26(6):766–776. doi: 10.1002/cpt1979266766. [DOI] [PubMed] [Google Scholar]
  11. Kishimoto A., Hollister L. E. Nortriptyline kinetics in Japanese and Americans. J Clin Psychopharmacol. 1984 Jun;4(3):171–172. doi: 10.1097/00004714-198406000-00036. [DOI] [PubMed] [Google Scholar]
  12. Küpfer A., Desmond P., Patwardhan R., Schenker S., Branch R. A. Mephenytoin hydroxylation deficiency: kinetics after repeated doses. Clin Pharmacol Ther. 1984 Jan;35(1):33–39. doi: 10.1038/clpt.1984.5. [DOI] [PubMed] [Google Scholar]
  13. Küpfer A., Roberts R. K., Schenker S., Branch R. A. Stereoselective metabolism of mephenytoin in man. J Pharmacol Exp Ther. 1981 Jul;218(1):193–199. [PubMed] [Google Scholar]
  14. Mahgoub A., Idle J. R., Smith R. L. A population and familial study of the defective alicyclic hydroxylation of debrisoquine among Egyptians. Xenobiotica. 1979 Jan;9(1):51–56. doi: 10.3109/00498257909034703. [DOI] [PubMed] [Google Scholar]
  15. Mbanefo C., Bababunmi E. A., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. A study of the debrisoquine hydroxylation polymorphism in a Nigerian population. Xenobiotica. 1980 Nov;10(11):811–818. doi: 10.3109/00498258009033811. [DOI] [PubMed] [Google Scholar]
  16. Mihaly G. W., Ward S. A., Edwards G., Orme M. L., Breckenridge A. M. Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol. 1984 Apr;17(4):441–446. doi: 10.1111/j.1365-2125.1984.tb02369.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rivera-Calimlim L., Reilly D. K. Difference in erythrocyte catechol-O-methyltransferase activity between Orientals and Caucasians: difference in levodopa tolerance. Clin Pharmacol Ther. 1984 Jun;35(6):804–809. doi: 10.1038/clpt.1984.116. [DOI] [PubMed] [Google Scholar]
  18. Spector R., Choudhury A. K., Chiang C. K., Goldberg M. J., Ghoneim M. M. Diphenhydramine in Orientals and Caucasians. Clin Pharmacol Ther. 1980 Aug;28(2):229–234. doi: 10.1038/clpt.1980.155. [DOI] [PubMed] [Google Scholar]
  19. Teng Y. S., Jehan S., Lie-Injo L. E. Human alcohol dehydrogenase ADH2 and ADH3 polymorphisms in ethnic Chinese and Indians of West Malaysia. Hum Genet. 1979;53(1):87–90. doi: 10.1007/BF00289455. [DOI] [PubMed] [Google Scholar]
  20. Woolhouse N. M., Andoh B., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther. 1979 Nov;26(5):584–591. doi: 10.1002/cpt1979265584. [DOI] [PubMed] [Google Scholar]

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