Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China.
Pharm Biol. 2010 Aug;48(8):947-52. doi: 10.3109/13880200903300220.
Lansoprazole is a gastric proton-pump inhibitor and has been demonstrated to be effective in the treatment of various peptic diseases. The effects of CYP2C19 activity on the pharmacokinetics of lansoprazole and its active metabolites in Chinese subjects have not previously been evaluated.
The study aimed to evaluate the effects of CYP2C19 activity in healthy Chinese volunteers.
Twenty-two healthy volunteers were recruited for an open trial and received a single dose of 30 mg lansoprazole. Using a validated LC-MS/MS method, we measured the plasma concentrations of lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone. The genotype of CYP2C19 was identified by polymerase chain reaction (PCR) analysis of single nucleotide polymorphisms (SNPs). Subjects were genotypically classified into the following three groups on the basis of PCR-SNP analysis for CYP2C19: homozygous EM (hmEM) group, heterozygous EM (htEM) group, and PM group. To test differences in pharmacokinetic parameters among the three groups, analysis of variance (ANOVA) after log-transformation of data was used.
Our results indicated that there were significant differences (p < 0.001) between the hmEM and PM groups, between the htEM and PM groups, and between the hmEM and htEM groups in C(max), AUC(0-t), and AUC(0-inf) of lansoprazole and lansoprazole sulfone. There were also significant differences (p < 0.001) between the hmEM and PM groups, and between the htEM and PM groups in C(max) of 5-hydroxylansoprazole.
兰索拉唑是一种胃质子泵抑制剂，已被证明可有效治疗各种消化性疾病。CYP2C19 活性对中国受试者中兰索拉唑及其活性代谢物药代动力学的影响尚未得到评估。
本研究旨在评估 CYP2C19 活性对健康中国志愿者的影响。
招募了 22 名健康志愿者进行开放性试验，并接受了 30mg 兰索拉唑的单次剂量。使用经过验证的 LC-MS/MS 方法，我们测量了兰索拉唑、5-羟基兰索拉唑和兰索拉唑砜的血浆浓度。CYP2C19 的基因型通过聚合酶链反应（PCR）分析单核苷酸多态性（SNP）进行鉴定。根据 PCR-SNP 分析，受试者被分为 CYP2C19 的三种基因型：纯合型 EM（hmEM）组、杂合型 EM（htEM）组和 PM 组。为了测试三组之间药代动力学参数的差异，对数转换后的数据采用方差分析（ANOVA）进行分析。
我们的结果表明，hmEM 和 PM 组之间、htEM 和 PM 组之间以及 hmEM 和 htEM 组之间在兰索拉唑和兰索拉唑砜的 C(max)、AUC(0-t)和 AUC(0-inf)方面存在显著差异（p < 0.001）。在 5-羟基兰索拉唑的 C(max)方面，hmEM 和 PM 组之间以及 htEM 和 PM 组之间也存在显著差异（p < 0.001）。
