INFLUENCE OF THE ROUTE OF ADMINISTRATION ON THE PHARMACOKINETICS OF PIRPROFEN ENANTIOMERS IN THE RAT

The pharmacokinetics of the enantiomers of the non-steroidal anti-infl ammatory drug pirprofen were studied in male Sprague-Dawley rats after oral and intravenous (iv) doses of the racemate. No significant diffe rences were detected between the enantiomers after oral or iv dosing i n t1/2, Vd, or SIGMAXu. However, the R:S area under the plasma concent ration (AUC) ratio after oral doses (0.92 +/- 0.13) was slightly but s ignificantly lower than after matching iv doses (1.05 +/- 0.036). The absolute bioavailability of the active S-enantiomer (78.5%) after oral doses was higher than the inactive R-enantiomer (69.3%). The plasma p rotein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S-enan tiomer was less bound than the R-enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The d ependency of the AUC ratio of the enantiomers on the route of administ ration may be due to stereoselective first-pass metabolism.