蛇床子素药动学特征及其代谢产物研究进展

Advances in Pharmacokinetic Characteristics and Metabolites of Osthole

蛇床子素(osthol,Ost)为香豆素类的一种天然药物成分,其不溶于水和半衰期短导致其生物利用度差,经肠道吸收快速分布其他组织。该文从蛇床子素的体内过程、药动学特征、靶向性、代谢产物等方面进行综述。蛇床子素在体内代谢的物质和体外模拟肝代谢的物质不大相同,蛇床子素经Ⅰ相代谢后产生去甲基蛇床子素、脱氢蛇床子素和羟基化蛇床子素等,有研究证明,经体内代谢检测尿液和粪便中没有脱氢产物,但有其他研究表明,血液、尿液中可以检测到,只是尿液中脱氢产物含量少,体外孵育肝代谢中有脱氢产物,可能脱氢蛇床子素是体内的活性代谢产物。明确蛇床子素在体内外的代谢特征及产物,有助于寻找体内活性代谢产物。

Osthol is a natural drug component of coumarins. It is insoluble in water and has a short half-life,resulting in poor bioavailability. It is absorbed through the intestine and distributed rapidly in other tissues. This paper reviews the in vivo process,pharmacokinetics,targeting and metabolites of Osthol. The substances metabolized by Osthol in vivo are not the same as those simulating liver metabolism in vitro. After phase Ⅰ metabolism,Osthol produces demethylated osthol,dehydrogenated Osthol and hydroxylated Osthol. Some studies have proved that there are no dehydrogenated products in urine and feces through in vivo metabolism detection. However other studies have shown that they can be detected in blood and urine,with lower the content of dehydrogenated products in urine,and there are dehydrogenated products in liver metabolism after incubation in vitro. It is possible that dehydrogenated Osthol is an active metabolite in vivo. Clarifying the metabolic characteristics and products of Osthol in vivo and in vitro is helpful to find active metabolites.