Metabolic inversion of stereoisomeric ibuprofen in man.

Metabolic stereoisomeric inversion of ibuprofen has both toxicological and clinical implications, and may represent a potential pitfall for patients with metabolic disorders. For those patients, reduced renal clearance in conjunction with metabolic bioactivation resulting from inversion may increase the plasma levels of the active species to an unpredictable degree. This will give rise to enhanced adverse consequences from the same mechanism as its antiinflammatory action, via inhibition of prostaglandin formation. In this study, an enantioselective HPLC technique has been established to scrutinize this unique biotransformation. It was found that ibuprofen epimerization in humans in virtually irreversible, from R to S, which is in agreement with the previous reports. Also, using rats as a model, we have prepared active subcellular hepatic preparations to effect this biotransformation. The "2-arylpropionyl-CoA epimerase" readily converts R-ibuprofen-CoA into its S-counterpart. Examination of the epimerase activity in various tissues indicated that this metabolism mainly occurred in the liver and kidney.