This poster was presented at the AAPS Annual Meeting in November of 2016.
Drug-induced liver toxicity is one of the most common adverse drug effects, and formation of reactive metabolites (RM) could be a contributing factor. Troglitazone (TGZ), the model compound used in this study, was withdrawn from the market due to a high incidence of liver failure. The metabolism of TGZ is known to generate RM, which were detected as stable glutathione (GSH) conjugates in vivo and in vitro. We previously reported application of stable isotope-labeled (SIL) GSH methodology to trap and detect RM of TGZ generated in cryopreserved human hepatocytes in suspension. A major finding was different degrees of incorporation of exogenous GSH/SIL-GSH mixture into trapped RM. More recently, we have also reported evidence, obtained using oil-filtration methodology, in support of one of the hypothesized mechanisms: differential efflux of RM from cryopreserved human hepatocyte suspensions, followed in some cases by extracellular trapping as GSH conjugates. The aim of this work was to investigate if efflux of RM is also intrinsic to primary cultures of human hepatocytes.