部分药物对华法林在大鼠肝微粒体中代谢的影响

Effects of some drugs on metabolism of warfarin in rats liver microsome

目的观察部分药物对华法林在大鼠肝微粒体中代谢的影响。方法选择在临床上可能与华法林合用的药物,如瑞舒伐他汀、辛伐他汀、硝苯地平、甲苯磺丁脲、罗红霉素、雷尼替丁和左氧氟沙星。分别将其与华法林在大鼠肝微粒体系中共孵育,采用高效液相色谱法测定华法林的浓度。结果瑞舒伐他汀和辛伐他汀对华法林代谢有抑制作用,与对照组相比有显著差异(P<0.05)。瑞舒伐他汀和辛伐他汀对华法林抑制的IC50值分别为17.53和4.87μmol·L-1,且剂量依赖性抑制华法林的代谢,抑制率分别为6%～32%和18%～47%。其他药物对华法林代谢无显著影响。结论瑞舒伐他汀和辛伐他汀可能抑制华法林在大鼠肝微粒体中的代谢。

AIM microsome. METHODS To observe the influence of some drugs on the metabolism of warfarin in rats liver The drugs that might be co-administrated with warfarin were selected, such as rosuvastatin, simvastatin, nifedipine, tolbutamide, roxithromycin, ranitidine, and levofloxacin. Warfarin was incubated with each drug in rats liver microsome. The residual concentration of warfarin in rat liver microsomal incubates was determined by high-performance liquid chromatography. RESULTS Rosuvastatin and simvastatin had significant inhibition on metabolism of warfarin （P 〈 0.05）. The ICso of rosuvastatin and simvastatin for the metabolism of warfarin were 17.53 and 4.87μmol·L^-1, respectively. The inhibition was concentrationdependence, and the inhibition ratio were 6% - 32% and 18% - 47% respectively. The other drugs had no significant inhibition on metabolism inhibition on metabolism of warfarin in of warfarin. CONCLUTION Rosuvastatin and simvastatin may have rats liver microsome