In vitro Drug Metabolism and Pharmacokinetics of a Novel Thiazolidinedione Derivative, a Potential Anticancer compound

Publication date: Available online 18 November 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Shankar Sengottuvelan, Vsuneetha VuppuAbstractThiazolidinediones are known for their activity against Type 2 diabetes and are currently being repurposed for their potent anti-cancer activity. In the present study, we have assessed in vitro metabolic properties and in vivo pharmacokinetic parameters of a novel thiazolidinedione derivative, BIT-15-67, a potential anticancer compound. BIT-15-67 showed low solubility in aqueous buffers at different pH values. The permeability was determined across the Caco-2 monolayer and BIT-15-67 showed high permeability and an efflux ratio of less than 2 suggesting that it is not a substrate of the efflux transporters (P-gp & BCRP). The plasma protein binding was evaluated by equilibrium dialysis and the compound exhibited moderate binding to mouse and rat plasma proteins. BIT-15-67 was stable (half-life> 30 min.) in mouse, rat, dog and human liver microsomes and unstable (half-life <15 min.) in rat hepatocytes suggesting possible Phase II metabolism. Liquid chromatography-tandem mass spectrometry was used to identify Phase I and Phase II metabolites. One of each Phase I and Phase II metabolites have been identified in rat hepatocytes samples. The BIT-15-67 is not an inhibitor of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4.The PK parameters were determined in both male and female Wistar rats after single intravenous dos...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research