Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug

Author(s): Wei Song, Meilin Liu, Junjun Wu, Hong Zhai, Yong Chen*, Zhihong Peng*.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 2 , 2019

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Graphical Abstract:


Background: Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong antiproliferative activity on all 60-National Cancer Institute (NCI) cancer cell lines. However, the widespread use of triptolide in the clinical practice is greatly limited for its multi-organ toxicity and narrow therapeutic window. All the toxic characteristics of triptolide are associated with the pharmacokinetics especially its distribution and accumulation in the target organ.

Methods: The literature review was done using PubMed search, SciFinder and Google Scholar databases with specific keywords such as triptolide, pharmacokinetics, drug-drug interaction, transporters, metabolism, modification to collect the related full-length articles and abstracts from 2000 to 2018.

Results: Oral triptolide is rapidly and highly absorbed. Grapefruit juice affects oral absorption, increasing the area under the concentration-time curve (AUC) by 153 % and the maximum concentration (Cmax) by 141 %. The AUC and the Cmax are not dose proportional. Triptolide distributes into the liver, heart, spleen, lung and kidney. Biotransformation of triptolide in rats includes hydroxylation, sulfate, glucuronide, N-acetylcysteine (NAC) and Glutathione (GSH) conjugation and combinations of these pathways. Less than 4 % of triptolide was recovered from the feces, bile and urine within 24 h. After repeating dosage, triptolide was eliminated quickly without accumulation in vivo. As a substrate of P-glycoprotein (P-gp) and CYP3A4, triptolide could have clinically significant pharmacokinetic interactions with those proteins substrates/inhibitors.

Conclusion: The findings of this review confirm the importance of pharmacokinetic character for understanding the pharmacology and toxicology of triptolide.

Keywords: Triptolide, pharmacokinetics, toxicity, metabolism, drug-drug interaction, antitumor.

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Year: 2019
Page: [147 - 154]
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DOI: 10.2174/1389200219666180816141506
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