Tassaneeyakul W, Vannaprasaht S, Yamazoe Y
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Br J Clin Pharmacol. 2000 Feb;49(2):139-44. doi: 10.1046/j.1365-2125.2000.00122.x.
To determine the effect of grapefruit juice on omeprazole metabolism in vivo.
This was a randomized crossover study with a 2 week washout period. Omeprazole (20 mg) was taken orally by 13 healthy volunteers after an overnight fast with either grapefruit juice or water. Serial blood samples were obtained over 12 h and standardized meals were served 3 and 10 h after the administration of omeprazole. Plasma concentrations of omeprazole and its major metabolites, 5-hydroxyomeprazole and omeprazole sulphone, were determined by high performance liquid chromatography (h.p.l.c.).
Mean area under the plasma concentration vs time curve (AUC) between 0 and 12 h for omeprazole sulphone was approximately 20% lower (P<0.01) in the group receiving grapefruit juice. There was no significant difference in the mean AUC of 5-hydroxyomeprazole or omeprazole. The AUC ratio of omeprazole sulphone to omeprazole, an index of CYP3A4 activity, was decreased by 33% (P<0.001) after administration of grapefruit juice whereas the AUC ratio of 5-hydroxyomeprazole to omeprazole, an index of CYP2C19 activity, did not differ between the two phases of the study. Although the time to peak concentration (tmax ) and terminal half-life (t1/2,z) of omeprazole and its two main metabolites were not altered, the peak concentration (Cmax ) of omeprazole sulphone was significantly reduced after administration of grapefruit juice.
Administration of grapefruit juice decreased the formation of omeprazole sulphone but not 5-hydroxyomeprazole. These results indicate that activities of CYP3A4, but not of CYP2C19, are inhibited by the simultaneous administration of grapefruit juice.
确定葡萄柚汁对奥美拉唑体内代谢的影响。
这是一项随机交叉研究，洗脱期为2周。13名健康志愿者在禁食过夜后，分别饮用葡萄柚汁或水后口服奥美拉唑（20毫克）。在12小时内采集系列血样，并在服用奥美拉唑后3小时和10小时提供标准化餐食。采用高效液相色谱法（h.p.l.c.）测定血浆中奥美拉唑及其主要代谢产物5-羟基奥美拉唑和奥美拉唑砜的浓度。
在接受葡萄柚汁的组中，奥美拉唑砜在0至12小时的血浆浓度-时间曲线下平均面积（AUC）约低20%（P<0.01）。5-羟基奥美拉唑或奥美拉唑的平均AUC无显著差异。葡萄柚汁给药后，作为CYP3A4活性指标的奥美拉唑砜与奥美拉唑的AUC比值降低了33%（P<0.001），而作为CYP2C19活性指标的5-羟基奥美拉唑与奥美拉唑的AUC比值在研究的两个阶段之间没有差异。尽管奥美拉唑及其两种主要代谢产物的达峰时间（tmax）和末端半衰期（t1/2,z）没有改变，但葡萄柚汁给药后奥美拉唑砜的峰浓度（Cmax）显著降低。
饮用葡萄柚汁减少了奥美拉唑砜的形成，但未减少5-羟基奥美拉唑的形成。这些结果表明，同时饮用葡萄柚汁可抑制CYP3A4的活性，但不抑制CYP2C19的活性。
