灵芝酸的药物代谢动力学研究进展

Pharmacokinetics of ganoderic acids

灵芝酸(ganoderic acid,GA)是传统名贵中草药灵芝的主要活性成分,是一类结构高度氧化的四环三萜类羊毛甾烷型衍生物,具有多种重要的药理活性,如抗肿瘤、调节免疫、抗氧化、抗糖尿病及抗HIV等。目前,有关灵芝酸的研究主要集中在生物合成、发酵调控、分离纯化、结构鉴定和药理药效等方面,与临床应用密切相关的药物代谢动力学研究还相对偏少。近年来研究表明,GA口服后,可经胃肠道迅速吸收并广泛分布于各组织器官,在肝脏发生Ⅰ相和Ⅱ相代谢后,主要经胆汁排泄。该文对GA的药代动力学特征及其吸收、分布、代谢和排泄过程进行较为系统的梳理,以期为灵芝三萜类药物的应用开发研究及临床合理用药提供科学依据。

Ganoderic acid(GA) is one of main bioactive components produced by Ganoderma lucidum,which a traditional Chinese herbal medicine and a kind of tracyclic triterpene lanosterol derivatives with highly oxidized structure. It has a variety of important pharmacological activities,such as anticancer,immunoregulation,anti-oxidation,anti-diabetes and anti-HIV. At present,the studies of GA mainly focus on biosynthesis,fermentation control,isolation and purification,structure identification and pharmacological effects.However,there are a fewer pharmacokinetic studies of GA,although it is closely related to the clinical application. Recent studies have shown that GA can be absorbed rapidly by gastrointestinal tract and distributed in various tissues and organs after oral intake. GA is metabolized by liver at phase Ⅰ and phase Ⅱ,and then mainly excreted by bile. In this paper,the pharmacokinetic characteristics of GA and its absorption,distribution,metabolism and excretion(ADME) will be systematically summarized,in order to provide scientific basis for the application and development studies of Ganoderma triterpenoid drugs and their rational clinical use.