Probenecid-induced changes in the clearance of carprofen enantiomers: a preliminary study.

Probenecid inhibits the elimination of several acidic drugs. In this study, the influence of probenecid on the pharmacokinetics of carprofen was investigated in three healthy volunteers after single peroral administration of 150 mg of RS-(+/-)-carprofen. Carprofen enantiomers and their glucuronides (after cleavage with sodium hydroxide) were measured by use of a stereospecific procedure. The plasma concentrations of S-(+)-carprofen were higher than those of R-(-)-carprofen at most of the sampling points. Probenecid reduced apparent total and renal clearances for both enantiomers. It also reduced the clearances of the carprofen enantiomers to their glucuronides and the renal clearances of the glucuronides. The differences caused by probenecid were significant, but few stereoselective effects were observed.