CYP2C19基因型对雷贝拉唑在健康人中药动学的影响

目的:研究雷贝拉唑在体内的代谢与CYP2C19酶的相关性,预测CYP2C19基因多态性对雷贝拉唑抑酸效应的影响。方法:采用开放、对照研究。根据PCR-RFLP方法确定的CYP2C19基因型将36例志愿者分为2组,CYP2C19强代谢型(EMs)组(n=24)及弱代谢型(PMs)组(n=12)。给予雷贝拉唑20mg单剂量口服,收集服药后12h的血样,用高效液相色谱(HPLC)法测定雷贝拉唑及其代谢产物硫醚雷贝拉唑、去甲基硫醚雷贝拉唑的血药浓度并作药动学分析。结果:硫醚雷贝拉唑的tmax和t1/2为EMs组(3.0±s0.6)h和(1.9±0.4)h;PMs组(3.6±0.9)h和(3.0±0.8)h,P<0.05和P<0.01,雷贝拉唑、硫醚雷贝拉唑以及去甲基硫醚雷贝拉唑的cmax,AUC,Cl/F2组差异均无显著意义。结论:雷贝拉唑的代谢主要不依赖于CYP2C19酶。

CYP2C19 genotype and its relation to pharmacokinetics of rabeprazole in healthy subjects

AIM: To explore whether in vivo human metabolic disposition of rabeprazole is dependent on CYP2C19 enzyme and to predict the influence of CYP2C19 genetic polymorphism on the acid-inhibitory efficacy of rabeprazole. METHODS: An open, comparative study of thirty-six healthy subjects genotyped for CYP2C19 by allele-specific polymerase chain reaction amplification was carried out and separated into 2 groups: EMs group(n=24) and PMs group(n=12). After administration of a single oral dose of rabeprazole 20 mg, blood samples were collected at various time-points until 12 h after administration. The plasma concentrations of rabeprazole with its two metabolites were measured by high-performance liquid chromatography (HPLC) and the pharmacokinetics disposition of them was analyzed. RESULTS: There were no significant differences between the two groups on c_(max) and AUC; but the mean t_(max) and t_(1/2) of thioether-rabeprazole in PMs (3.6±s 0.9) h and (3.0±0.8) h were significantly longer than those in EMs (3.0±0.6) h and (1.9±0.4) h(P<0.05 and P<0.01). CONCLUSION: The pharmacokinetics of rabeprazole is independent on CYP2C19 and rabeprazole is dominantly transformed to the thioether metabolite in a nonenzymatical manner.