甲硝唑对兰索拉唑在大鼠体内药动学的影响

Effects of metronidazole on the pharmacokinetics of lansoprazole in rat

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。

OBJECTIV To evaluate the effect of metronidazole on the metabolism of lansoprazole in rats in vivo. METHODS plasma concentrations of lansoprazole and its metabolite 5-hydroxylansoprazole and lansoprazole sulfone were determined by LC/MS/MS, and the pharmacokinetical parameters of these three compounds were calculated. RESULTS The pharmacokinetical parameters showed that metronidazole （200 mg·kg^-1 ） decreased AUC0-4h of lansoprazole （0. 20 ± 0. 06）（P〈0. 05）, significantly increased the ratios of 5-hydroxylansoprazole/lansoprazole AUC0-4h from （0. 24± 0. 08） to （0. 39 ±0. 19） （P〈0. 05）. CONCLUSION This study indicated that in rats metronidazole might not inhibit the metabolism of lansoprazole by CYP3A4, but it might induce the activity of CYP2C19.