Oral bioavailability and pharmacokinetics of the new insulin sensitizer DRF-2189 in Wistar rats

The pharmacokinetics of the new insulin sensitizing agent, DRF-2189 ([5-[4- [2-(1-indolyl) ethoxy]phenyl]methyl] thiazolidine-2,4-dione, CAS 172647-53- 9) were studied in male Wistar rats following oral doses of 1, 3 and 10 mg/ kg as suspension in 0.25% carboxymethylcellulose. Drug was extracted from p lasma samples using a solvent mixture containing ethylacetate and dichlorom ethane (3:2) and analyzed by high-performance liquid chromatography with fl uorescence detection. DRF-2189 was absorbed slowly, attaining maximum level s at 2-3 h, and was eliminated with a half-life (t(1/2)) of about 3 h. The C-max and AUC((0-infinity)) increased linearly (r(2) = 0.99) with the dose, while the elimination half-life (t(1/2)) was independent of the dose. An i ntravenous pharmacokinetic study of DRF-2189 was carried out in Wistar rats at a dose of 3.0 mg/kg. The pharmacokinetic parameters AUC((0-infinity)), t(1/2), plasma clearance (Cl) and volume of distribution (V-d) were found t o be 49.52 mu g x h/ml, 2.99 h, 16.31 ml/h and 45.11 mi, respectively. Oral bioavailability (f) of DRF-2189 in Wistar rats was 44%. Based on pharmacok inetic studies, DRF-2189 is a good choice for further development.