摘要
目的探讨异烟肼(INH)与利福平(RFP)合用致肝毒性增加的部分作用机理。方法采用在体心脏灌流法获取小鼠原代肝细胞,将其常规培养5d后,分别用含INH(87.5μmol.L-1)和INH+RFP(87.5μmol.L-1+48.6μmol.L-1)培养液培养48h,液相色谱-电喷雾质谱联用法测定2组培养液中INH及其代谢产物乙酰肼(Acetylhydrazine,AHZ)和肼(Hydrazine,HZ)的浓度。结果与INH组比较,INH+RFP组AHZ和HZ浓度增加,有显著性差异(P<0.01)。结论RFP和INH合用后使INH肝毒性代谢物浓度增加,可能是其肝毒性增加的原因之一。
Aim To investigate the mechanism of isoniazid （INH）and rifampicin（RFP）. Methods Mouse hepatocytes were obtained through cardio-perfusion in mice and isolated by two-step in situ collagenase perfusion methods, after five days of culture of mouse hepatocytes, the culture hquid was replaced by INH（87.5μmol.L^-1 ） , INH ＋ RFP（87.5μmol.L^-1 ＋48.6μmol.L^-1 ）. the concentration of AHZ and HZ was determined by LC/ESI-MS in 48h. Results The concentration of AHZ and HZ increased more in the INH ＋ RFP group than in the INH group（ P 〈 0.01 ）. Conclusion RFP can increase the concentration of acetylhydrazine （AHZ） and （ hydrazine ） HZ, which may increase the hepatotoxicity of INH.
出处
《解放军药学学报》
CAS
2009年第5期414-416,共3页
Pharmaceutical Journal of Chinese People's Liberation Army
关键词
异烟肼
利福平
代谢
isoniazid
rifampicin
metabolism
