The 2-arylpropionic acid nonsteroidal anti-inflammatory drugs are usually administered as racemates. The enantiomers may have different pharmacokinetics and the R-isomer may metabolically invert to the S-isomer. To pinpoint the kinetics of the inversion and the location in which this metabolic process takes place, racemic ketoprofen (KT) was administered to the rat. Using a stereospecific HPLC assay, the pharmacokinetics of KT were studied following 10 mg/kg iv, po, and ip doses of racemic KT to male Sprague-Dawley rats. Plasma concentrations were always greater for (S)-KT than for (R)-KT. The mean +/- SD AUC S/R ratios were 11.8 +/- 9.93 (N = 5), 11.0 +/- 2.64 (N = 4), and 33.7 +/- 11.2 (N = 5) after iv, ip, and po doses, respectively. Bile duct-cannulated rats (N = 4) had AUCs of 85.4 +/- 58.6 and 22.8 +/- 18.4 (mg/liter) hr for (S)- and (R)-KT, respectively. The percentage of conjugated drug recovered in bile was 77.9 +/- 3.77 and 11.4 +/- 2.48% of the dose as (S)- and (R)-KT, respectively. The data indicate 1) substantial stereoselectivity, 2) presystemic gastrointestinal and systemic inversion of (R)- to (S)-KT, 3) extensive elimination of drug through bile in rats, and 4) extensive reabsorption subsequent to biliary excretion.