Marinac J S, Balian J D, Foxworth J W, Willsie S K, Daus J C, Owen R, Flockhart D A
Department of Medicine, University of Missouri-Kansas City, School of Medicine 64108, USA.
Clin Pharmacol Ther. 1996 Aug;60(2):138-44. doi: 10.1016/S0009-9236(96)90129-0.
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.
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 were measured for phenotype determination. Identification of CYP2C19m1 genotypes were performed with use of the polymerase chain reaction.
Results were 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 (m1/m1) in exon 5 of CYP2C19. Twenty-eight of the extensive metabolizers were heterozygous (m1/wt) and the remaining 70 were homozygous (wt/wt). No side effects were reported.
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.
我们的目标是研究奥美拉唑作为单剂量口服探针在确定黑人受试者CYP2C19表型中的应用，并确定表型与基因型之间的相关性。
这项单剂量、开放标签的门诊研究在一家社区型大学附属医院门诊进行。研究对象为100名未服用任何药物的健康、无亲缘关系的黑人成年人（年龄范围18至50岁）。测量基线奥美拉唑、服药后2小时的奥美拉唑和5'-羟基奥美拉唑浓度以确定表型。使用聚合酶链反应进行CYP2C19m1基因型鉴定。
获得了28名男性和72名女性的结果。发现98名受试者为表型广泛代谢者，两名是慢代谢者（一名男性；一名吸烟者）。基因型测定显示，两名奥美拉唑慢代谢者在CYP2C19第5外显子中存在单碱基对突变的纯合子（m1/m1）。28名广泛代谢者为杂合子（m1/wt），其余70名是纯合子（wt/wt）。未报告有副作用。
居住在美国中西部的这一健康黑人人群中CYP2C19慢代谢者的患病率为2%，与白人受试者和津巴布韦绍纳人群中报告的患病率相似，但远低于亚洲受试者。奥美拉唑是一种安全且特异的CYP2C19酶系统探针，与基因型相关性良好。
