The CYP2C19 enzyme polymorphism

Pharmacology

Volumn 61, Issue 3, 2000, Pages 174-183

  Wedlund, Peter J ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Disease risk; Genotype; Mephenytoin 4' hydroxylase; Molecular modeling; Pharmacogenetics; Phenotype

Indexed keywords

ALPRAZOLAM; CARISOPRODOL; CITALOPRAM; CLOMIPRAMINE; CLOZAPINE; CYTOCHROME P450 2C19; DESIPRAMINE; DIAZEPAM; FLUVOXAMINE; GLIBENCLAMIDE; HEXOBARBITAL; IMIPRAMINE; LANSOPRAZOLE; LOSARTAN; MEPHENYTOIN; MEPROBAMATE; METHYLPHENOBARBITAL; MOCLOBEMIDE; NICERGOLINE; NORDAZEPAM; OMEPRAZOLE; PANTOPRAZOLE; PHENYTOIN; PROGUANIL; PROPRANOLOL; TETRABAMATE; TRIAZOLAM; WARFARIN;

BLADDER CARCINOMA; CHRONIC LIVER DISEASE; CLINICAL RESEARCH; DISEASE ASSOCIATION; DRUG METABOLISM; DRUG RESPONSE; ENZYME CONFORMATION; ENZYME POLYMORPHISM; ETHNIC DIFFERENCE; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; LIVER TOXICITY; LUNG CANCER; MOLECULAR MODEL; PARKINSON DISEASE; POPULATION RESEARCH; PRIORITY JOURNAL; PROSTATE CARCINOMA; REVIEW; SCLERODERMA; SQUAMOUS CELL CARCINOMA; SYSTEMIC LUPUS ERYTHEMATOSUS;

EID: 0033828454     PISSN: 00317012     EISSN: None     Source Type: Journal    
DOI: 10.1159/000028398     Document Type: Review

References (106)

1. Küpfer A, Desmond P, Schenker S, Branch R: Family study of a genetically determined deficiency of mephenytoin hydroxylation in man (astract). Pharmacologist 1979;21:173.
2. Küpfer A, Desmond P, Patwardhan R, Schenker S, Branch RA: Mephenytoin hydroxylation deficiency: Kinetics after repeated doses. Clin Pharmacol Ther 1984;35:33-39.
3. Ward SA, Goto F, Nakamura K, Jacqz E, Wilkinson GR, Branch RA: S-mephenytoin 4-hydroxylase is inherited as an autosomal-recessive trait in Japanese families. Clin Pharmacol Ther 1987;42:96-99.
4. Brøsen K, deMorais SMF, Meyer UA, Goldstein JA: A multifamily study on the relationship between CYP2C19 genotype and S-mephenytoin oxidation phenotype. Pharmacogenetics 1995;5:312-317.
5. Alván G, Bechtel P, Iselius L, Gundert-Remy U: Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 1990;39:533-537.
6. Sohn D-R, Kusaka M, Ishizaki T, Shin S-G, Jang I-J, Shin J-G. Chiba K: Incidence of S-mephenytoin hydroxylation deficiency in a Korean population in the interphenotypic differences in diazepam pharmacokinetics. Clin Pharmacol Ther 1992;52:160-169.
7. Weerasuriya K, Jayakody RL, Smith CAD, Wolf CR, Tucker GT, Lennard MS: Debrisoquine and mephenytoin oxidation in Sinhalese: A population study. Br J Clin Pharmacol 1994; 38:466-470.
8. Xie H-G Xu Z-H, Luo X, Huang S-L, Zeng F-D, Zhou H-H: Genetic polymorphisms of debrisoquine and S-mephenytoin oxidation metabolism in Chinese populations: A meta-analysis. Pharmacogenetics 1996;6:235-238.
9. Xie HG, Kim RB, Stein CM, Wilkinson GR, Wood AJJ: Genetic polymorphism of (S)-mephenytoin 4′-hydroxylation in populations of African descent. Br J Clin Pharmacol 1999;48: 402-408
10. Tamminga WJ, Wemer J, Oosterhuis B, Wieling J, Wilffert B, de Leij LFMH, de Zeeuw RA, Jonkman JHG: CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: Indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol 1999;55:177-184.
11. Aynacioglu AS, Sachse C, Bozkurt A, Kortunay S, Nacak M, Schröder T, Kayaalp SO, Roots I, Brockmöller J: Low frequency of detective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 1999;66:185-192.
12. Xie H-G, Stein CM, Kim RB, Wilkinson GR, Flockhart DA, Wood AJJ: Allelic. genotypic and phenotypic distributions of S-mephenytoin 4′-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics 1999; 9:539-549.
13. Kaneko A, Lum JK, Yaviong L, Takahashi N, Ishizaki T, Bertilsson L, Kobayakawa T, Bjorkman A: High and variable frequencies of CYP2C19 mutations: Medical consequences of poor metabolism in Vanuatu and other Pacific islands. Pharmacogenetics 1999;9:581-590.
14. Wrighton SA, Stevens JC, Becker GW, Vanden Branden M: Isolation and characterization of human liver cytochrome P450 2C19: Correlation between 2C19 and S-mephenytoin 4′-hydroxylation. Arch Biochem Biophys 1993;306: 240-245.
15. Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Rauci JL, Lasker JM, Ghanayem BI: Evidence that CYP2C19 is the major (S)-mephenytoin 4′-hydroxylase in humans. Biochemistry 1994;33:1743-1752.
16. De Morais SMF, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA: The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Sci 1994;269:15419-15422.
17. de Morais SMF, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA: Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 1994;46: 594-598.
18. Xiao A-S, Goldstein JA, Xie H-G. Blaisdell J, Wang W, Jiang C-H, Yan F-X, He N, Huang S-L, Xu Z-H, Zhou HH: Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther 1997;281:604-609.
19. Ferguson RJ, de Morais SMF, Benhamou S, Bouchardy C, Blaisdell J, Ibeanu G, Wilkinson GR, Sarich TC, Wright JM, Dayer P, Goldstein JA: A new genetic detect in human CYP2C19: Mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther 1998;284:356-361.
20. Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics 1998;8: 129-135.
21. Ideanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer B, Ghanayem BI, Blaisdell J: Identification of new human CYP2C19 Alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther 1998;286:1490-1495.
22. Ideanu GC, Blaisdell J, Ferguson RJ, Ghanayem BI, Brøsen K, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Goldstein JA: A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. J Pharmacol Exp Ther 1999; 290:635-640.
23. Küpfer A, Branch RA: Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. Clin Pharmacol Ther 1985;38:414-418.
24. Bertilsson L, Henthorn TK, Sanz E, Tybring G, Säwe J, Villén T: Importance of genetic factors in the regulation of diazepam metabolism: Relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin Pharmacol Ther 1989;45:348-355.
25. Adedoyin A, Prakash C, O'Shea D, Blair IA, Wilkinson GR: Stereoselective disposition of hexobarbital and its metabolites: Relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. Pharmacogen 1994; 4:27-38.
26. Sohn D-R, Kwon J-T, Kim H-K, Ishizaki T: Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4′-hydroxylation phenotype status. Clin Pharmacol Ther 1997; 61:574-582.
27. Setiabudy R, Kusaka M, Chiba K, Darmansjah I, Ishizaki T: Metabolic disposition of proguanil in extensive and poor metabolisers of S-mephenytoin 4′-hydroxylation recruited from an Indonesian population. Br J Clin Pharmacol 1995;39:297-301
28. Skjelbo E, Brøsen K, Hallas J, Gram LF: The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clin Pharmacol Ther 1991;49: 18-23.
29. Andersson T, Regårdh C-G, Lou Y-C, Zhang Y, Dahl M-L, Bertilsson L: Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects. Pharmacogenetics 1992;2:25-31.
30. Helsby NA, Ward SA, Edwards G, Howells RE, Breckenridge AM: The pharmacokinetics and activation of proguanil in man: Consequences of variability in drug metabolism. Br J Clin Pharmacol 1990;30:593-598.
31. Sindrup SH, Brøsen K, Hansen MG, Aaes-Jorgensen T, Overo KF, Gram LF: Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther Drug Monitor 1993;15:11-17.
32. Dahl M-L, Llerena A, Bondesson U, Lindström L, Bertilsson L: Disposition of clozapine in man: Lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms. Br J Clin Pharmacol 1994;37:71-74.
33. Gram LF, Guentert TW, Grange S, Vistisen K, Brøsen K: Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19. CYP2D6, and CYP1A2: A panel study. Clin Pharmacol Ther 1995;57:670-677.
34. Tanaka M, Ohkubo T, Otani K, Suzuki A, Kaneko S, Sugawara K, Ryokawa Y, Hakusui H, Yamamori S, Ishizaki T: Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4′-hydroxylation phenotype and genotype. Clin Pharmacol Ther 1997;62:619-628.
35. Tanaka M, Yamazaki H, Hakusui H, Nakamichi N, Sekino H: Differential stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor in extensive and poor metabolizers of pantoprazole: A preliminary study. Chirality 1997;9:17-21.
36. Dalén P, Alvan G, Wakelkamp M, Olsen H: Formation of meprobamate for cardisoprodol is catalysed by CYP2C19. Pharmacogenetics 1996;6:387-394.
37. Böttiger Y, Dostert P, Benedetti MS, Bani M, Fiorentini F, Casati M, Poggesti I, Alm C, Alvan G, Bertilsson L: Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans. Br J Clin Pharmacol 1996; 42:707-711.
38. Hooper WD, Qing MS: The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans. Clin Pharmacol Ther 1990;48:633-640.
39. Yasui N, Otani K, Ohkubo T, Osanai T, Sugarwara K, Chiba K, Ishizaki T, Kaneko S: Single-dose pharmacokinetics and pharmacodynamics of oral triazolam in relation to cytochrome P4502C19 (CYP2C19) activity.
40. Dahl-Puustinen ML, Alm C, Bertilsson L, Christenson I, Östman J, Thunberg E, Wikström I: Lack of relationship between glibenclamide metabolism and debrisoquine or mephenytoin hydroxylation phenotypes. Br J Clin Pharmacol 1990;30:476-480.
41. Spigset O, Granberg K, Hägg S, Norström A, Dahlqvist R: Relationship between fluvoxamine pharmacokinetics and CYP2D6/ CYP2C19 phenotype polymorphisms. Eur J Clin Pharmacol 1997;52:129-133.
42. Ieiri I, Mamiya K, Urae A, Wada Y, Kimura M, Irie S, Amamoto T, Kubota T, Yoshioka S, Nakamura K, Nakano S, Tashiro N, Higuchi S: Stereoselective 4′-hydroxylation of phenytoin: Relationship to (S)-mephenytoin polymorphism in Japanese. Br J Clin Pharmacol 1997; 43:441-445.
43. Sandwall P, Lo M-W, Jonzon B, Dalén P, Furtek C, Ritter M, Alván G, McCrea J, Sjöqvist F: Lack of polymorphism of the conversion of losartan to its active metabolite E-3174 in extensive and poor metabolizers of debrisoquine (cytochrome P450 2D6) and mephenytoin (cytochrome P450 2C19). Eur J Clin Pharmacol 1999;55:279-283.
44. Kaisary A, Smith P, Jaczq E, McAllister CB, Wilkinson GR, Ray WA, Branch RA: Genetic predisposition to bladder cancer: Ability to hydroxylate debrisoquine and mephenytoin as risk factors. Cancer Res 1987;47:5488-5493.
45. May DG, Black CM, Olsen JN, Csuka ME, Tanner SB, Bellino L, Porter JA, Wilkinson GR. Branch RA: Scleroderma is associated with differences in individual routes of drug metabolism: A study with dapsone, debrisoquin, and mephenytoin. Clin Pharmacol Ther 1990;48:286-295.
46. Gudjonsson P, Sanz E, Alván G, Aquilonius SM, Reviriego J: Poor hydroxylator phenotypes of debrisoquine and S-mephenytoin are not over-represented in a group of patients with Parkinson's disease. Br J Clin Pharmacol 1990; 30:301-302.
47. Tsuneoka Y, Fukushima K, Matsuo Y, Ichikawa Y, Watanabe Y: Genotype analysis of the CYP2C19 gene in the Japanese population. Life Sci 1996;59:1711-1715.
48. Benhamou S, Bouchardy C, Dayer P: Lung cancer risk in relation to mephenytoin hydroxylation activity. Pharmacogenetics 1997;7: 157-159.
49. Wadelius M, Autrup JL, Stubbins MJ, Andersson S-O, Johansson J-E, Wadelius C, Wolf CR, Autrup H, Ranc A: Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTPI and their association with prostate cancer. Pharmacogenetics 1999;9:333-340.
50. Kortunay S, Bozkurt A, Bathum L, Basci NE, Calgüneri M, Brøsen K, Kayaalp SO: CYP2C19 genotype does not represent a genetic predisposition in idiopathic systemic lupus erythematosus. Ann Rheum Dis 1999;58:182-185.
51. Lewis DFV, Lake BG: Molecular modeling and quantitative structure-activity relationship studies on the interaction of omeprazole with cytochrome P450 isozymes. Toxicology 1998; 125:31-44.
52. Lewis DFV, Dickins M, Weaver RJ, Eddershaw PJ, Goldfarb PS, Tarbit MH: Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: Rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily. Xenobiotica 1998;28:235-268.
53. Lewis DFV: Homology modeling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity. Exp Toxicol Pathol 1999;51:369-374.
54. Wilkinson GR, Guengerich FP, Branch RA: Genetic polymorphism of S-mephenytoin hydroxylation. Pharmacol Ther 1989;43:53-76.
55. Sohn DR, Shin SG, Ishizaki T: S-mephenytoin pharmacogenetics and its clinical implications in Asian ethnic populations. Asia Pacific J Pharmacol 1994;9:287-301.
56. Bertilsson L: Geographical/Interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromcs P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 1995;29: 192-209.
57. Daniel HI, Edeki TI: Genetic polymorphism of S-mephenytoin 4′-hydroxylation. Psychopharmacol Bull 1996;32:219-230.
58. Wedlund PJ, Aslanian WS, Jacqz E, McAllister CB, Branch RA, Wilkinson GR: Phenotypic differences in mephenytoin pharmacokinetics in normal subjects. J Pharmacol Exp Ther 1985;234:662-669.
59. Wedlund PJ, Aslanian WS, McAllister CB, Wilkinson GR, Branch RA: Mephenytoin hydroxylation deficiency in Caucasians: Frequency of a new oxidativc drug metabolism polymorphism. Clin Pharmacol Ther 1984;36:773-780.
60. Jacqz E, Hall SD, Branch RA, Wilkinson GR: Polymorphic metabolism of mephenytoin in man: Pharmacokinetic interaction with a co-regulated substrate, mephobarbital. Clin Pharmacol Ther 1986;39:646-653.
61. Wedlund PJ, Sweetman BJ, Wilkinson GR, Branch RA: Pharmacogenetic association between the formation of 4-hydroxymephenytoin and a new metabolite of S-mephenytoin in man. Drug Metab Disp 1987;15:277-279.
62. Zhang Y, Blouin RA, McNamara PJ, Steinmetz J, Wedlund PJ: Limitation to the use of the urinary S-/R-mephenytoin ratio in pharmacogenetic studies. Br J Clin Pharmacol 1991; 31:350-352.
63. Tybring G, Bertilsson L: A methodological investigation on the estimation of the S-mephenytoin hydroxylation phenotype using the urinary S/R ratio. Pharmacogenetics 1992;2:241-243.
64. Tybring G, Nordin J, Bergman T, Bertilsson L: An S-mephenytoin cysteine conjugate identified in urine of extensive but not of poor metabolizers of S-mephenytoin. Pharmacogenetics 1997;7:355-360.
65. Balian JD, Suknova N, Harris JW, Hewett J, Pickle L, Goldstein JA, Woosley RL, Flockhart DA: The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: A population study. Clin Pharmacol Ther 1995;57: 662-669.
66. Wedlund PJ, Wilkinson GR: In vivo and in vitro measurement of CYP2C19 activity. Methods Enzymol 1996;272:105-114.
67. Marinac JS, Balian JD, Foxworth JW, Willsie SK, Daus JC, Owen R, Flockhart DA: Determination of CYP2C19 phenotype in Black Americans with omeprazole: Correlation with genotype. Clin Pharmacol Ther 1996:60:138-144.
68. Roh HK, Dahl ML, Tybring G, Yamada H, Cha YN, Bertilsson L: CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics 1996;6: 547-551.
69. Riddell DC, Wang H, Umbenhauer DR, Beaume PH, Guengerich FP, Hamerton JL: Regional assignment for the genes encoding human P450IIIA3 (CYP3A) and P450IIC9 (CYP2C) (abstract). Cytogenet Cell Genet 1987;46:682.
70. Gray IC, Nobile C, Muresu R, Ford S, Spurr NK: A 2.4 megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. Genomics 1995;28:328-332.
71. de Morais SMF, Goldstein JA, Xie H-G, Huang S-L, Lu Y-Q, Xiao Z-S, Ile N, Zhou H-H: Genetic analysis of the S-mephenytoin polymorphism in a Chinese population. Clin Pharmcol Ther 1995;58:404-411.
72. Roh HK, Dahl ML, Johansson I, Ingelman-Sundberg M, Cha YN, Bertilsson L: Debrisoquine and S-mephenytoin hydroxylation phenotypcs and genotypes in a Korean population. Pharmacogenetics 1996;6:441-447.
73. Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM, Evans DA: Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 1997;7:59-64.
74. Garcia-Barceló M, Chow L-Y, Chiu HFK, Wing YK, Lee DTS, Lam KL, Wave MMY: Frequencies of defective CYP2C19 alleles in a Hong Kong Chinese population: Detection of the rare allele CYP2C19*4. Clin Chem 1999; 45:2273-2274.
75. Lamba JK, Dhiman RK, Kohli KK: Genetic polymorphism of the hepatic cytochrome P450 2C19 in North Indian subjects. Clin Pharmacol Ther 1998;63:422-427.
76. Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA: Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 1985;38:402-408.
77. Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou H-H, Zhou B-J, Liao C-L, Zhang L-M: Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland China. Clin Pharmacol Ther 1989;46:198-207.
78. Doshi BS, Kulkarni RD, Chauhan BL: Frequency of impaired mephenytoin 4′-hydroxylation in an Indian population. Br J Clin Pharmacol 1990;30:779-780.
79. Evans DAP, Krahn P, Narayanan N: The mephenytoin (cytochrome P450 2C 19) and dextromethorphan (cytochrome P450 2D6) polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics 1995;5:64-71.
80. Cavalli-Sforza LL, Menozzi P, Piazza A: The History and Geography of Human Genes: Australia, New Guinea, and the Pacific Islands. Princeton, Princeton University Press, 1994.
81. Kumana CR, Lauder IJ, Chan M, Ko W, Lin HJ: Differences in diazepam pharmacokinetics in Chinese and white Caucasians relation to body lipid stores. Eur J Clin Pharmacol 1987; 32:211-215.
82. Setiabudy R, Chiba K, Kusaka M, Ishizaki T: Caution in the use of a 100 mg dose of racemic mephenytoin for phenotyping Southeastern Oriental subjects. Br J Clin Pharmacol 1992: 33:665-666.
83. 12 in patients on long-term omeprazole treatment. Aliment Pharmacol Ther 1999;13:453-458.
84. Caraco Y, Lagerstrom P-O, Wood AJJ: Ethnic and genetic determinants of omeprazole disposition and effect. Clin Pharmacol Ther 1996; 60:157-167.
85. Ward SA, Helsby NA, Skjelbo E, Brøsen K, Gram LF, Breckenridge AM: The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism: A panel study. Br J Clin Pharmacol 1991;31:689-692.
86. Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Bjorkman A: Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis 1999; 179:974-979.
87. Skjelbo E, Mutabingwa TK, Bygbjerg I, Nielsen KK, Gram LF: Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians. Clin Pharmacol Ther 1996;59:304-311.
88. Black C, May G, Csuka ME, Lupoli S, Wilkinson GR, Branch RA: Activity of oxidative routes of metabolism of debrisoquin, mephenytoin, and dapsone is unrelated to the pathogenesis of vinyl chloride-induced disease. Clin Pharmacol Ther 1992;52:659-667.
89. Ranek L, Dalhoff K, Poulsen HE, Brøsen K, Flachs H, Loft S: Drug metabolism and genetic polymorphism in subjects with previous halothane hepatitis. Scand J Gastroenterol 1993; 28:677-680.
90. Arthur H, Dahl ML, Siwers B, Sjøvist F: Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia. J Clin Psychopharmacol 1995;15:211-216.
91. Horsmans Y, Lannes D, Pessayre D, Larrey D: Possible association between poor metabolism of mephenytoin and hepatotoxicity caused by Atrium®, a fixed combination preparation containing phenobarbital, febarbamate and difebarbamate. J Hepatol 1994;21:1075-1079.
92. Spigset O, Hedenmalm K, Dahl ML, Wiholm BE, Dahlqvist R: Seizures and myoclonus associated with antidepressant treatment: Assessment of potential risk factors, including CYP2D6 and CYP2C19 polymorphisms, and treatment with CYP2D6 inhibitors. Acta Psychiatr Scand 1997;96:379-384.
93. Bathum L, Andersen-Ranberg K, Boldsen J, Brøsen K, Jeune B: Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevity. Eur J Clin Pharmacol 1998;54:427-430.
94. Kimura M, Ieiri I, Mamiya K, Urae A, Higuchi S: Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monitor 1998; 20:243-247.
95. Zhang Y, Reviriego J, Lou Y-Q, Sjöqvist F, Bertilsson L: Diazepam metabolism in native Chinese poor and extensive hydroxylators of S-mephenytoin: Interethnic differences in comparison with white subjects. Clin Pharmacol Ther 1990;48:496-502.
96. Wan J, Xia H, He N, Lu Y-Q, Zhou HH: The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype. Br J Clin Pharmacol 1996;42: 471-474.
97. Qin XP, Xie HG, Wang W, He N, Huang SL, Xu ZH, Ou-Yang DS, Wang YJ, Zhou HH: Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects. Clin Pharmacol Ther 1999;66:642-646.
98. Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lundborg P: Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clin Pharmacol Ther 1990;47:79-85.
99. Sohn D-R, Kobayashi K, Chiba K, Lee K-H, Shin S-G, Ishizaki T: Disposition kinetics and metabolism of omeprazole in extensive and poor metabolizers of S-mephenytoin 4′-hydroxylation recruited from an Oriental population. J Pharmacol Exp Ther 1992;262: 1195-1202.
100. Ishizaki T, Sohn DR, Kobayashi K, Chiba K, Lee KH, Shin SG, Andersson T, Regardh CG, Lou YC, Zhang Y: Interethnic differences in omeprazolc metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals. Ther Drug Monitor 1994;16:214-215.
101. Caraco Y, Lagerstrom P-O, Wood AJJ: Ethnic and genetic determinants of omeprazole disposition and effect. Clin Pharmacol Ther 1996:60:157-167.
102. Morinobu S, Tanaka T, Kawakatsu S, Totsuka S, Koyama E, Chiba K, Ishizaki T, Kubota T: Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy. Psychiatr Clin Ncurosci 1997;51:253-257.
103. Ward SA, Walle T, Walle K, Wilkinson GR, Branch RA: Propranolol's metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities. Clin Pharmacol Ther 1989;45:72-79.
104. Xie HG, Xu ZH, Huang SL, Liu JH, Wu JX, Jiang CH, Zhou HH: No correlation between side-chain of propranolol oxidation and S-mephenytoin 4′-hydroxylase activity. Chung Kuo Yao Li Hsueh Pao 1997;18:216-218.
105. Otani K, Ysui N, Kaneko S, Ohkubo T, Osanai T, Sugawara K, Hayashi K, Chiba K, Ishizaki T: Effects of genetically determined S-mephenytoin 4-hydroxylation status and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam. Neuropsychopharmacology 1997;16:8-14.
106. Takahashi H, Kashima T, Nomizo Y, Muramoto N, Shimizu T, Nasu K, Kubota T, Kimura S, Echizen H: Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin Pharmacol Ther 1998;63:519-528.