Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug.

Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug. Curr Drug Metab. 2018 Aug 16;: Authors: Song W, Liu M, Wu J, Zhai H, Chen Y, Peng Z Abstract Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong anti-proliferative activity on all 60-national cancer institute (NCI) cancer cell lines. The antitumor property of triptolide has made it become a promising anti-cancer drug. 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. The article presents a comprehensive review of the preclinical pharmacokinetics of triptolide. 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...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research