Simulation of interindividual differences in inactivation of reactive para-benzoquinone imine metabolites of diclofenac by glutathione S-transferases in human liver cytosol.

•DF-1′,4′-QI and DF-2,5-QI are efficiently inactivated by multiple major (hepatic) GST isoforms at low and physiological GSH concentrations.•GSTM1-1 and P1-1 can prevent alkylation of a model nucleophile by DF-1′,4′-QI and DF-2,5-QI in vitro.•Based on the GST-profiles in a panel of 22 individual human livers, a large inter-individual variability in detoxification of DF-1′,4′-QI and DF-2,5-QI is predicted.•A low hepatic activity of GSTs might be considered as risk factor for DF-induced IDILI.