摘要
目的研究细胞色素P4503A5*3、多药耐药基因C3435T和细胞色素P450 2C19*2突变对兰索拉唑(抗胃酸药)药代动力学的影响。方法24名健康志愿者单次口服兰索拉唑30 mg后,用HPLC方法测定血浆中的兰索拉唑浓度,研究在中国汉族健康人中兰索拉唑的体内过程与基因型的相关性。结果细胞色素P4502C19*1/*1与*2/* 2比较,AUC_(0-∞)存在显著性差异(P=0.04),表达CYP2C19*2/*2的受试者体内兰索拉唑的暴露量是*1/*1者的1.75倍;MDR1 3435C与3435TT比较,t_(max)、AUC_(0-2)存在显著性差异(P=0.026,P=0.03),但总暴露量(AUC_(0-∞))2组间没有差异,表明CYP3A5*3各基因型间药代动力学参数不存在显著性差异。结论CYP2C19*2/*2突变使兰索拉唑体内暴露量增大;MDR1 3435TT基因型者兰索拉唑起始吸收速率较大,达峰快;但该基因型对其总吸收量没有影响,CYP3A5*3对兰索拉唑药代动力学没有影响。
Objective To study the relationship of CYP3A5 ＊ 3, MDR1 C3435T and CYP2C19 ＊ 2 genetic polymorphisms in Chinese healthy volunteers and the pharmacokinetics of lansoprazole. Methods Thirty milligrams of lansoprazole was orally administered to 24 healthy Chinese subjects, and blood samples were taken after dosing. The polymorphie alleles of CYP3A5 ＊ 3, MDR1 C3435T and CYP2C19 ＊ 2 in each subject were determined. The whole blood concentration of lansoprazole were measured by an HPLC. Results Lansoprazole AUC0-∞ significantly difference between CYP2C19 ＊ 1/＊ 1 and ＊ 2/＊ 2 genotypes groups. The mean AUC0-∞ ratio of lansoprazole between CYP2C19 ＊ 1/＊ 1 and ＊ 2/ ＊2 was 1 ： 1.75. tmax and AUC0-2 of lansoprazole were statistically significant difference between the MDR1 3435C and 3435TT genotypes（P = 0.026, P = 0.03 ）. However no difference was found in geometric means AUC0-∞ of lansoprazole between the two genotypes. We did not found any significant difference between CYP3A5 ＊ 3 genotypes. Conclusion CYP2C19 activity was reduced in ＊ 2 homozygotes, and there was no effect of CYP3A5 ＊ 3 on lasoprazole pharmacokinetics.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2008年第6期497-500,共4页
The Chinese Journal of Clinical Pharmacology
