Determination of CYP2C19 phenotype in black Americans with omeprazole: Correlation with genotype

被引:50
作者
Marinac, JS
Balian, JD
Foxworth, JW
Willsie, SK
Daus, JC
Owen, R
Flockhart, DA
机构
[1] GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20057
[2] GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20057
[3] US FDA,WASHINGTON,DC 20204
关键词
D O I
10.1016/S0009-9236(96)90129-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype. Methods: This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic, Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications, Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations mere measured for phenotype determination, Identification of CTP2C19(ml) genotypes were performed with use of the polymerase chain reaction. Results: Results mere obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker), Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m(1)/m(1)) in exon 5 of CTP2C19, Twenty-eight of the extensive metabolizers were heterozygous (m(1)/wt) and the remaining 70 were homozygous (wt/wt), No side effects were reported, Conclusions: The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects, Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype.
引用
收藏
页码:138 / 144
页数:7
相关论文
共 44 条
[1]   CLINICAL CONSEQUENCES OF POLYMORPHIC DRUG OXIDATION [J].
ALVAN, G .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1991, 5 (03) :209-228
[2]   POLYMORPHIC HYDROXYLATION OF S-MEPHENYTOIN AND OMEPRAZOLE METABOLISM IN CAUCASIAN AND CHINESE SUBJECTS [J].
ANDERSSON, T ;
REGARDH, CG ;
LOU, YC ;
ZHANG, Y ;
DAHL, ML ;
BERTILSSON, L .
PHARMACOGENETICS, 1992, 2 (01) :25-31
[3]   SLOW OMEPRAZOLE METABOLIZERS ARE ALSO POOR S-MEPHENYTOIN HYDROXYLATORS [J].
ANDERSSON, T ;
REGARDH, CG ;
DAHLPUUSTINEN, ML ;
BERTILSSON, L .
THERAPEUTIC DRUG MONITORING, 1990, 12 (04) :415-416
[4]   THE HYDROXYLATION OF OMEPRAZOLE CORRELATES WITH S-MEPHENYTOIN METABOLISM - A POPULATION STUDY [J].
BALIAN, JD ;
SUKHOVA, N ;
HARRIS, JW ;
HEWETT, J ;
PICKLE, L ;
GOLDSTEIN, JA ;
WOOSLEY, RL ;
FLOCKHART, DA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 57 (06) :662-669
[5]   IMPORTANCE OF GENETIC-FACTORS IN THE REGULATION OF DIAZEPAM METABOLISM - RELATIONSHIP TO S-MEPHENYTOIN, BUT NOT DEBRISOQUIN, HYDROXYLATION PHENOTYPE [J].
BERTILSSON, L ;
HENTHORN, TK ;
SANZ, E ;
TYBRING, G ;
SAWE, J ;
VILLEN, T .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (04) :348-355
[6]   ENANTIOSELECTIVE AMITRIPTYLINE METABOLISM IN PATIENTS PHENOTYPED FOR 2 CYTOCHROME-P450 ISOZYMES [J].
BREYERPFAFF, U ;
PFANDL, B ;
NILL, K ;
NUSSER, E ;
MONNEY, C ;
JONZIERPEREY, M ;
BAETTIG, D ;
BAUMANN, P .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 52 (04) :350-358
[7]   A MULTIFAMILY STUDY ON THE RELATIONSHIP BETWEEN CYP2C19 GENOTYPE AND S-MEPHENYTOIN OXIDATION PHENOTYPE [J].
BROSEN, K ;
DEMORAIS, SMF ;
MEYER, UA ;
GOLDSTEIN, JA .
PHARMACOGENETICS, 1995, 5 (05) :312-317
[8]   GENETICALLY-DETERMINED DEBRISOQUINE OXIDATION CAPACITY IN BLADDER-CANCER [J].
CARTWRIGHT, RA ;
PHILIP, PA ;
ROGERS, HJ ;
GLASHAN, RW .
CARCINOGENESIS, 1984, 5 (09) :1191-1192
[9]   Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: Comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype [J].
Chang, M ;
Dahl, ML ;
Tybring, G ;
Gotharson, E ;
Bertilsson, L .
PHARMACOGENETICS, 1995, 5 (06) :358-363
[10]   INTERPHENOTYPE DIFFERENCES IN DISPOSITION AND EFFECT ON GASTRIN-LEVELS OF OMEPRAZOLE - SUITABILITY OF OMEPRAZOLE AS A PROBE FOR CYP2C19 [J].
CHANG, M ;
TYBRING, G ;
DAHL, ML ;
GOTHARSON, E ;
SAGAR, M ;
SEENSALU, R ;
BERTILSSON, L .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1995, 39 (05) :511-518