Influence of probenecid on the urinary excretion rates of the diastereomeric benoxaprofen glucuronides.

A major biotransformation pathway for many NSAIDs from the group of optically active 2-arylpropionic acids is the conjugation with D-glucuronic acid, forming diastereomers. These conjugates of the S-(+)-and the R-(-)-enantiomers can be separated directly, e.g., by ion-pair chromatography on a C18-column using a mixture of tetrabutylammonium buffer pH 2.5 and acetonitrile as mobile phase. In man about 40% of the dose was recovered in urine as glucuronides (ratio S:R = 2.2) within 96 hours of p.o. administration of racemic drug. When probenecid, which is known to influence the elimination of several acidic drugs, was administered in addition, the amount excreted as glucuronides during 4 days was clearly reduced. Furthermore, the enantiomeric ratio was changed significantly, possibly because of an increase of stereoinversion due to the reduced drug clearance.