尼莫地平在人肝微粒体内的代谢

:采用人肝微粒体在体外研究尼莫地平 (Nim)在人体内的代谢物及代谢途径 . Nim在人肝微粒体内被迅速代谢成 3个代谢物 ,分别是 Nim二氢吡啶环脱氢代谢物 M1,二氢吡啶环侧链脱甲基代谢物M2 ,二氢吡啶环脱氢及其侧链脱甲基代谢物 M3.Nim在人肝微粒体中的最初的两步代谢反应是其二氢吡啶环脱氢氧化及其侧链脱甲基反应 ,两者的代谢产物可以被进一步代谢为代谢物 M3.CYP3A的特异性抑制剂醋竹桃霉素和酮康唑可以抑制Nim的二氢吡啶环脱氢氧化及其侧链脱甲基反应 ,使 Nim的代谢速率明显下降 ,结果提示 CYP3A参与了 Nim在人肝微粒体内的代谢

Metabolism of nimodipine in human liver microsomes

The metabolism of nimodipine(Nim) in human liver microsomes was studied in vitro to identify its metabolites and metabolic pathway. Nim was rapidly metabolized and three metabolites of Nim were isolated and identified in human liver microsomes. These are dehydrogenated metabolite of dihydropyridine ring of Nim (M 1), demethylated metabolite of lateral chain of dihydropyridine ring of Nim (M 2) and the dehydrogenated and demethylated metabolite of Nim (M 3), respectively. The initial two metabolic reactions of Nim in human liver microsomes were the dehydrogenation of dihydropyridine ring of Nim and demethylation of lateral chain of dihydropyridine ring of Nim. The metabolite M 1 and M 2 can be further metabolized to form metabolite M 3. Troleandomycin and ketoconazole ,the specific inhibitors of CYP3A, can inhibit the dehydrogenation and demethylation of Nim and significantly lower the rate of metabolism of Nim. The results suggested that CYP3A involve the metabolism of Nim in human liver microsomes.