Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans

AIM： To observe the pharmacokinetics and pharmacodynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS： The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups： homozygous extensive metabolizers （homEM）, heterozygous extensive metabolizers （hetEM） and poor metabolizers （PM）. After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS： The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION： In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.

瞄准：观察 rabeprazole 的 pharmacokinetics 和药效学并且在不同 CYP2C19 遗传型组比较浆液促胃液素集中。方法：中国汉健康志愿者的 CYP2C19 遗传型地位被聚合酶链反应限制碎片长度多型性方法决定。二十个 H pylori 否定的健康题目自愿参予了学习。他们被划分成下列三个组：同型结合的广泛的 metabolizers (homEM ) ，异质接合的广泛的 metabolizers (het 他们) 和差的 metabolizers (下午) 。在他们口头上地收到了 rabeprazole 以后在 d 的早上从前每日的 20 mg 1 并且 d 8，在管理和胃内 pH 价值被 Digitrapper pH 为 24 h 监视以后，血样品在各种各样的时间点被收集直到 24 h。浆液促胃液素集中被放射性免疫测定测量。rabeprazole 的浆液集中被高效液相色谱法测量。结果：为在一个单身者和多次量后面的 rabeprazole 的吝啬的 AUC 价值在 homEM 和下午组之间，然而并非在 homEM 和 het 他们之间是显著地不同的，否则 het 他们和下午组织。在胃内 pH medians 的有效差量都没在单次量或多次量以后在三个不同遗传型组之中被观察。在 d 之间的 pH medians 的比率 1 并且 d 8 从 84% ～ 108%。吝啬的促胃液素 AUC 价值在三个遗传型组之中也是不同的，与在单次量以后的 1.0， 1.2 和 1.5 的相对比率， 1.0， 1.5 和 1.6 分别地在在 homEM， het 他们和下午的多次量以后组织。在三个不同遗传型组之中的促胃液素 AUC 价值也没在单次量或多次量以后显示出有效差量。有更低的胃内酸味的题目显示出更高的浆液促胃液素层次和 rabeprazole 的集中。结论：在中国汉健康的人， rabeprazole 的 pharmacokinetics 依赖于 rabeprazole 和促胃液素水平的 CYP2C19 遗传型地位，而是酸禁止的功效没显著地被影响。