Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 左中教授 (药剂学院) |
| 胡少君博士 (药剂学院) |
| 张玉峰博士 (药剂学院) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1208/s12248-014-9664-x |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/2WOS source URL
其它资讯
摘要Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V (max), K (m), and Cl-int of 47.5 +/- 3.4 nmol/min/mg, http://aims.cuhk.edu.hk/converis/portal/Publication/204 +/- http://aims.cuhk.edu.hk/converis/portal/Publication/2http://aims.cuhk.edu.hk/converis/portal/Publication/2 mu M, and http://aims.cuhk.edu.hk/converis/portal/Publication/233 +/- 9 mu l/min/mg with intestinal microsomes and http://aims.cuhk.edu.hk/converis/portal/Publication/2.9http://aims.cuhk.edu.hk/converis/portal/Publication/2 +/- 0.07 nmol/min/mg, http://aims.cuhk.edu.hk/converis/portal/Publication/2http://aims.cuhk.edu.hk/converis/portal/Publication/2.7 +/- 1.http://aims.cuhk.edu.hk/converis/portal/Publication/2 mu M, and 1http://aims.cuhk.edu.hk/converis/portal/Publication/29 +/- 4 mu l/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-http://aims.cuhk.edu.hk/converis/portal/Publication/2.4 mg/kg, r (http://aims.cuhk.edu.hk/converis/portal/Publication/2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.
着者Gao Q, Zhang YF, Wo SK, Zuo Z
期刊名称AAPS JOURNAL
出版年份http://aims.cuhk.edu.hk/converis/portal/Publication/2014
月份11
日期1
卷号16
期次6
出版社SPRINGER
页次13http://aims.cuhk.edu.hk/converis/portal/Publication/21 - 1333
国际标準期刊号1550-7416
语言英式英语
关键词arctigenic acid; arctigenin; arctigenin-4 '-O-glucuronide; pharmacokinetics; semi-mechanistic pharmacokinetic modeling
Web of Science 学科类别Pharmacology & Pharmacy
