R)-2-Arylpropionates are often inverted to the pharmacologically active S-enantiomers in vivo, although there is significant interspecies variability in inversion. In order to provide a basis for determining the biochemical consequences of this unique process using rats as a model, it was important to establish the pharmacokinetic disposition of the enantiomers of ibuprofen, a drug well inverted in man and flurbiprofen, a drug apparently poorly inverted in man. Rats were dosed i.v. with a single dose of (R)-or (S)-ibuprofen (20 mgkg), (R,S)ibuprofen (40 mgkg), (R)or (S)-flurbiprofen (10 mgkg), or (R,S)-flurbiprofen (20 mg/kg). Each treatment group consisted of six animals. Serial blood samples were withdrawn over a period of 6 h for ibuprofen and 10 h for flurbiprofen. These drugs were assayed in plasma by a stereospecific HPLC assay. The pharmacokinetics of the ibuprofen and flurbiprofen enantiomers were evaluated using a twocompartment open model with conversion of the R-to S-enantiomers in the central compartment. There was 50 * 4% inversion of (R)-ibuprofen, a figure similar to that observed in man and (Rhibuprofen had a higher clearance (12.6 * 1.3 ml/ min/kg) than (Sbibuprofen (7.7 * 0.7 ml/min/kg; P C 0.01). The clearance of (R)flurbiprofen after racemate (2.3 k 0.1 ml/min/kg) was higher than its clearance when administered alone (1.7 & 0.2 ml/min/kg; P < 0.011, indicating a pharmacokinetic interaction between the enantiomers (most probably at plasma protein binding sites). A corresponding difference was not observed for ibuprofen. There was a small amount of inversion of (R)-flurbiprofen as determined by area analysis (4.5 5 1.6%). However, this calculation may be in some error because of the interaction between the enantiomers. These data demonstrate quantitative similarities in the inversion of ibuprofen and flurbiprofen in rats and man, a useful basis for comparing the effects of these two drugs on fatty acid metabolism.