课件：PRT与NSAID导致的消化道黏膜损伤.ppt

不像其它的PPIs，雷贝拉唑主要是通过非酶代谢而形成到硫醚。肝细胞色素P450酶主要参与其它PPIs的代谢，不是雷贝拉唑主要的代谢途径. 在自愿者的研究表明，雷贝拉唑不与经肝脏氧化代谢的药物相互作用，包括茶碱，苯妥英，华法林和地西泮. 虽然不能预测在活体内的状态，体外研究表明，雷贝拉唑不与环孢霉素相互作用。在所有的PPIs中，奥美拉唑最有可能与其它药物相互作用. 那么临床上常用的阿斯匹林是否经CYP2C19 代谢呢？答案是肯定的。一项试验表明：低剂量阿斯匹林激活体内CYP2C19活性。所以与阿斯匹林和用时，为了不影响阿斯匹林的疗效，，要选择不经CYP2C19 代谢的PPI， 如雷贝拉唑。 The paper shows that low-dose aspirin induced the in vivo activities of CYP2C19 but did not affect the activities of CYP1A2, CYP2D6, and CYP2E1. The reference is below: 氯吡格雷也主要通过P450酶代谢 低剂量阿斯匹林激活体内CYP2C19活性 氯吡格雷与奥美拉唑同时服用，由于都通过CYP2C19代谢，氯吡格雷的有效性降低，从而增加心血管事件的发生机率4 Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. by: X. P. Chen, Z. R. Tan, S. L. Huang, Z. Huang, D. S. Ou-Yang, H. H. Zhou OBJECTIVE: This study was designed to define the effect of low-dose aspirin administration on the activity of cytochrome P450 (CYP) in normal human subjects. METHODS: Aspirin, 50 mg daily, was given for 14 days to 18 nonsmoking healthy male volunteers. A modified 5-drug cocktail procedure consisting of caffeine, mephenytoin, metoprolol, chlorzoxazone, and midazolam was performed to simultaneously assess in vivo activity of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A, respectively. The activities were assessed on 4 occasions including at baseline, after 7 and 14 daily doses of aspirin, and at 7 days after discontinuation of aspirin. Concentrations of parent drugs and corresponding metabolites in biologic samples were assayed by reversed-phase HPLC. RESULTS: Both 7-day and 14-day aspirin intake increased the activity of CYP2C19 significantly, as indicated by 4-hydroxymephenytoin urinary recovery (P .001). Induction of low-dose aspirin on CYP2C19 was time-dependent. CYP3A activity indices increased moderately but significantly by both 7-day and 14-day aspirin treatment (P .05), but the percentage changes in CYP3A activity indices were not significant. Low-dose aspirin had no effect on CYP1A2, CYP2D6, and CYP2E1 in vivo activity by either 7-day or 14-day t