Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.
Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.
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DOI：
10.3346/jkms.2017.32.5.729
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发表时间：
2017-05
影响因子：
4.5
通讯作者：
Choi SE
中科院分区：
文献类型：
--
作者：
Park S;Hyun YJ;Kim YR;Lee JH;Ryu S;Kim JM;Oh WY;Na HS;Lee JG;Seo DW;Hwang IY;Park Z;Jang IJ;Oh J;Choi SE
本研究的目的是研究细胞色素P450酶2基因C19*2和*3基因多态性对奥美拉唑药代动力学(PK)和药效学(PD)反应的影响。24名韩国健康志愿者口服奥美拉唑20 mg，每日1次，连续8天。筛选出CYP2C19单核苷酸多态(SNPs)(*2、*3、*17)的基因型。采用LC-MS/MS法测定血浆中奥美拉唑、奥美拉唑砜和5-羟基(5-羟基)奥美拉唑的血药浓度。PK参数的测定采用非隔室方法。计算平均pH的变化和胃pH>4.0的时间百分比(%)。在CYP2C19表型组中，代谢不良(PM)组的代谢率最低，奥美拉唑的AUC最高。PM组平均pH变化最大，胃pH>4.0的时间百分比最大。证实了奥美拉唑的AUC与胃pH>4.0的时间百分比之间的关系。研究表明，在韩国健康志愿者中，CYP2C19*2和*3对奥美拉唑的PKs和PDs有影响。临床试验登记在美国国立卫生研究院(https://clinicaltrials.gov)，编号NCT02299687。
The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. Clinical trial registry at the U.S. National Institutes of Health (https://clinicaltrials.gov), number NCT02299687.