利福定和利福平对小鼠肝微粒体酶的影响比较

利福定和利福平具有相似的化学结构,为了比较二者对肝微粒体酶的影响,我们考察了它们对小鼠体内安替比林血浆水平、戊巴比妥钠睡眠时间和肝脏重量的影响,测定了肝微粒体蛋白和细胞色素P-450含量及两种酶活性的改变,用凝胶电泳法比较了微粒体多肽组份相对含量的变化。结果表明,利福平在这些方面均表现出显著的肝微粒体酶诱导作用,而利福定则否。这提示利福定可能在临床很少导致严重的药物相互作用发生。

A COMPARISON OF EFFECTS OF RIFAMPIN AND RIFANDIN ON MOUSE HEPATIC MIXED FUNCTION OXIDASE SYSTEM

Rifandin (R761) is a new derivative of rifampin (RFP) developed and used in China for the chemotherapy of tuberculosis. It is well known that RFP is a potent inducer of hepatic mixed function oxidase system (HMFOS), but the effect of R761 on HMFOS is not definite. In present study, mice were pretreated with R761 or RFP 40 mg/kg day p. o. for 10 days. Compared to control group, we found that RFP significantly decreased mouse pentobarbital sleeping time and plasma antipyrine level in vivo; significantly increased the weight of mice livers, the content of liver microsomal protein and cytochrome P-450, the activity of NADPH-cytochro-me C reductase and NADPH oxidase. Although R761 significantly increased the weight of mice livers and the activity of these two enzymes, its effect on the other parameters was not significant. SDS-Polyacrylamide get electrophoresis (SDS-PAGE) of mice hepatocyte microsomal fraction showed that the proportion of polypeptides with molecular weight ranged from 41,000 to 69,000 dalton, was significantly increased compared to control following RFP pretreatment. R761 did not significantly affect the proportion of these polypeptides, in which the known cytochrome P-450 isoenzymes were included, but it did significantly decrease the proportion of polypeptide with about 132,000 molecular weight as well as RFP by the same SDS-PAGE procedure. The results suggested that RFP is a potent inducer of mouse HMFOS, but R761 exhibited only a weak inhibitory effect on HMFOS. So R761 may not cause serious drug interactions in clinical practice when it is combined with other drugs.