Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug.

Background: Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong anti-proliferative 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 (C-max) 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.