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目的:研究甲硝唑在大鼠体内对兰索拉唑药动学特征的影响。方法:通过对兰索拉唑及细胞色素P450酶2C19(CYP2C19)代谢产物5-羟基兰索拉唑和细胞色素P450酶3A4(CYP3A4)代谢产物兰索拉唑砜的血药浓度的测定,计算大鼠体内药动学参数,以甲硝唑联合兰索拉唑用药组与兰索拉唑单独用药组的AUC0-4h比值为指标,研究甲硝唑对大鼠体内兰索拉唑代谢的影响。结果:联用甲硝唑后,兰索拉唑的AUC0-4h降低为单独使用兰索拉唑组的(0.20±0.06)倍(P<0.05)。甲硝唑显著增加5-羟基兰索拉唑与兰索拉唑AUC0-4h的比值,从(0.24±0.08)增至(0.39±0.19)(P<0.05)。结论:甲硝唑在大鼠体内对兰索拉唑CYP3A4主导的磺化代谢抑制作用不明显,对CYP2C19主导的羟化代谢途径可能有诱导作用。
Objective: To study the effect of metronidazole on the pharmacokinetics of lansoprazole in rats. Methods: The plasma concentrations of lansoprazole sulfone, a metabolite of lansoprazole and cytochrome P450 2C19 (CYP2C19) metabolites 5-hydroxy-lansoprazole and cytochrome P450 enzyme 3A4 (CYP3A4), were calculated The pharmacokinetic parameters in rats were compared with the AUC0-4h ratio of metronidazole plus lansoprazole and lansoprazole alone to evaluate the effect of metronidazole on the metabolism of lansoprazole in rats . Results: After combined with metronidazole, lansoprazole AUC0-4h reduced to (0.20 ± 0.06) times (P <0.05) lansoprazole alone group. Metronidazole significantly increased the ratio of 5-hydroxy-lansoprazole to lansoprazole AUC0-4h from (0.24 ± 0.08) to (0.39 ± 0.19) (P <0.05). CONCLUSION: Metronidazole has little inhibitory effect on the sulfonation metabolism of lansoprazole CYP3A4 in rats, which may induce CYP2C19-induced hydroxylation pathway.