Pharmacokinetics of flobufen and its main active metabolite in the rat

Pharmacokinetic study of the anti-inflammatory [3H] flobufen (I) and its active metabolite (II) has been carried out in rats given po and iv doses of 2, 10, and 50 mg/kg I and equimolar doses of II. Various pharmacokinetic parameters of I and II [dose normalized AUC; mean residence time (MRT); systemic blood clearance; steady state volume of distribution, (Vss)] are dose-independent. I is completely absorbed from the gastrointestinal tract and is rapidly (MRT = 7.2 hr) converted to II, which is slowly (MRT = 2.6 days) eliminated from the blood. The fraction of total blood clearance that forms II is 0.83 following iv dose of I. The Vss of the less lipophilic metabolite II is somewhat lower (0.36-0.46 liters/kg) than that of the parent drug (0.51-0.56 liters/kg).