FIRST-PASS METABOLISM AND BILIARY RECIRCULATION OF DROLOXIFENE IN THEFEMALE SPRAGUE-DAWLEY RAT

1. Utilizing a validated ultrasensitive hplc assay (lower limit of qua ntitation 25 pg/ml), we characterized the disposition profile of drolo xifene in the female Sprague-Dawley rat following intravenous, oral an d intraportal administration. 2. The site and extent of first-pass met abolism and the extent of enterohepatic recirculation were investigate d. 3. Our findings suggest that the intestine is neither a metabolic n or an absorptive barrier to the bioavailability of droloxifene in the female Sprague-Daw ley rat and that first-pass hepatic extraction is a pproximately 70-80 % following an oral dose of 1 mg/kg. 4. Employment of a modified linked-rat model revealed that droloxifene is subject to enterohepatic recirculation (approximately 5 %) in the rat.