@article{APS8235,
author = {Jia Liu and Xin Zhou and Xiao-yan Chen and Da-fang Zhong},
title = {Excretion of [3H]triptolide and its metabolites in rats after oral administration},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {4},
year = {2016},
keywords = {},
abstract = {Jia LIU, Xin ZHOU, Xiao-yan CHEN, Da-fang ZHONG*
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Aim: To investigate the routes of elimination and excretion for triptolide recovered in rats.
Methods: After a single oral administration of [3H]triptolide (0.8 mg/kg, 100 μCi/kg) in Sprague Dawley rats, urine and fecal samples were collected for 168 h. To study biliary excretion, bile samples were collected for 24 h through bile duct cannulation. Radioactivity was measured using a liquid scintillation analyzer, and excretion pathway analysis was performed using an HPLC/on-line radioactivity detector.
Results: The total radioactivity recovered from the urine and feces of rats without bile duct ligation ranged from 86.6%–89.1%. Most of the radioactivity (68.6%–72.0%) was recovered in the feces within 72 h after oral administration, while the radioactivity recovered in the urine and bile was 17.1%–18.0% and 39.0%–39.4%, respectively. The HPLC/on-line radiochromatographic analysis revealed that most of the drug-related radioactivity was in the form of metabolites. In addition, significant gender differences in the quantity of these metabolites were found: monohydroxytriptolide sulfates were the major metabolites detected in the urine, feces, and bile of female rats, while only traces of these metabolites were found in male rats.
Conclusion: Radiolabeled triptolide is mainly secreted in bile and eliminated in feces. The absorbed radioactivity is primarily eliminated in the form of metabolites, and significant gender differences are observed in the quantity of recovered metabolites, which are likely caused by the gender-specific expression of sulfotransferases.
Keywords: triptolide; immunosuppressant; pharmacokinetics; excretion pathway; gender difference
This project was supported by grants from the Ministry of Science and Technology of China (2013ZX09507001, 2012ZX09301001-005, and 2014CB541906), the National Natural Science Foundation of China (81202341), and the Shanghai Commission of Science and Technology (12XD1402100 and 11ZR1408000)
* To whom correspondence should be addressed.
E-mail dfzhong@mail.shcnc.ac.cn
Received 2013-09-24 Accepted 2013-11-15},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/8235}
}