候选新药对大鼠肝细胞色素P4503A4影响的研究

The Effect of Anti-Ada Ocean Drug Candidate on CYP3A4

目的研究候选新药(HSH)对大鼠肝细胞色素P4503A4是否有抑制或诱导作用,以及这种作用是否具有性别差异。方法取大鼠雌雄各半,随机分为4个组:雄性对照组(Ⅰ)、雄性给药组(Ⅱ)、雌性对照组(Ⅲ)、雌性给药组(Ⅳ),均采用钙离子沉淀法制备肝微粒体。在各组肝微粒体中同时给予一定剂量的探针药物及目标药物,进行孵育,于不同时间点取样,测定该探针药物的剩余浓度并计算其体外半衰期。结果HSH对肝细胞色素P4503A4无影响。结论就大鼠而言,药物对肝细胞色素P4503A4无影响,HSH在同各种与CYP3A4代谢有关的药物合用时,相对安全。

OBJECTIVE The inhibitory or inducible effects of the ocean drug candidate on CYP3A4 in rats and their sex-based differences were studied. METHODS All rats, half in male and half in female, were divided into four groups randomly： male antitheses group（ Ⅰ ） ,male drug-added group（ Ⅱ ） ,female antitheses group（ Ⅲ ） ,female drug-added group（Ⅳ）. All liver microsome was prepared by calcium-ion deposition method. Both the probe drug and the drug candidate were added into different groups and incubated, The samples were selected at different time point and the residual concentration of probe drug Was demrmined. Furthermore, the t1/2 in vivo was calculated. RESULTS This drug had no significant effect on CYP3A4 in beth male and female rats. CONCLUSION As concern as rats ,this drug has no effect on CYP 3A4, it is relatively safe when it is used in future experiments ,or administrated with other drugs related to CYP3A4.