Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan.
Mol Biol Rep. 2012 Apr;39(4):4195-200. doi: 10.1007/s11033-011-1204-5. Epub 2011 Jul 17.
To relate the pharmacokinetics of orally administered lansoprazole in healthy adult Jordanian men with CYP2C19 polymorphisms and to determine the percentage of CYP2C19 polymorphism in Jordanian population and the allelic frequency of CYP2C192 and CYP2C193. A total of 78 healthy Jordanian volunteers were included in this study from three different bioequivalence studies, one of these studies which included 26 volunteers was done on lansoprazole. Genotyping for CYP2C191, CYP2C192, CYP2C193 was done for all 78 volunteers, the data of genotyping of all subjects used for screening the frequency of different genotypes and the allelic frequency of different polymorphisms in healthy Jordanian men, the pharmacokinetics and genotyping data for the study of lansoprazole was matched and compared to investigate presence of statistical differences in pharmacokinetic parameters. In Jordanian subjects, the allele frequencies of the CYP2C192 and CYP2C19*3 mutation were 0.16 and 0, respectively. The concentration-time curves in the two groups [homozygote extensive metabolizer (homEM, n = 19) and heterozygote extensive metabolizer (homEM, n = 7)] groups were fitted to a non-compartment model. In the homEM and in the hetEM groups, the main kinetic parameters were as follows: T(max) (2.1875 ± 0.777) and (2.54 ± 1.87) h, C(max) (697.875 ± 335) and (833.58 ± 436.26) mg/l, t(1/2) (1.3 ± 0.43) and (2.38 ± 1.64) h, AUC((0→∞)) were (1,684.9 ± 888) and (3,609.8 ± 318) mg h l(-1), respectively. The Jordanian population showed similarities in CYP2C19 allele and genotype distribution pattern with Caucasians and Africans. CYP2C19 allele and poor metabolizer (PM) genotype frequencies in the Jordanian population are distinct from populations' from East Asia such as Japanese and Koreans. Although lower pharmacokinetic parameters were found in homEM compared to hetEM but there was no significant difference between the two groups (P < 0.05).
研究约旦成年男性中 CYP2C19 多态性与口服兰索拉唑药代动力学的关系，并确定约旦人群中 CYP2C19 多态性的百分比以及 CYP2C192 和 CYP2C193 的等位基因频率。方法：本研究共纳入来自 3 项生物等效性研究的 78 名健康约旦志愿者，其中 1 项研究（包括 26 名志愿者）涉及兰索拉唑。对所有 78 名志愿者进行 CYP2C191、CYP2C192、CYP2C193 的基因分型。对所有受试者的基因分型数据进行筛选，以确定不同基因型的频率和健康约旦男性中不同多态性的等位基因频率。将兰索拉唑研究的药代动力学和基因分型数据进行匹配和比较，以研究药代动力学参数是否存在统计学差异。结果：在约旦受试者中，CYP2C192 和 CYP2C19*3 突变的等位基因频率分别为 0.16 和 0。两组[纯合子强代谢者（homEM，n=19）和杂合子强代谢者（homEM，n=7）]的浓度-时间曲线均拟合为非房室模型。在 homEM 和 hetEM 组中，主要动力学参数如下：T(max)（2.1875±0.777）和（2.54±1.87）h，C(max)（697.875±335）和（833.58±436.26）mg/L，t(1/2)（1.3±0.43）和（2.38±1.64）h，AUC((0→∞))为（1684.9±888）和（3609.8±318）mg·h·L(-1)。约旦人群的 CYP2C19 等位基因和基因型分布模式与白种人和非洲人相似。与东亚人群（如日本人和韩国人）相比，约旦人群的 CYP2C19 等位基因和弱代谢者（PM）基因型频率明显不同。尽管与 hetEM 相比，homEM 中的药代动力学参数较低，但两组间无显著性差异（P<0.05）。
