First-pass metabolism and biliary recirculation of droloxifene in the female Sprague-Dawley rat.
1. Utilizing a validated ultrasensitive hplc assay (lower limit of quantitation 25 pg/ml), we characterized the disposition profile of droloxifene in the female Sprague-Dawley rat following intravenous, oral and intraportal administration. 2. The site and extent of first-pass metabolism and the extent of enterohepatic recirculation were investigated. 3. Our findings suggest that the intestine is neither a metabolic nor an absorptive barrier to the bioavailability of droloxifene in the female Sprague-Dawley rat and that first-pass hepatic extraction is approximately 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.
Nickerson
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Drug Metabolism Department, Pfizer Inc., Groton, CT 06340, USA.
Tess
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Toler
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D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004764:Enterohepatic Circulation; D004965:Estrogen Antagonists / Q000493:pharmacokinetics*; D005260:Female; D007275:Injections, Intravenous; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D004965:Estrogen Antagonists; D013629:Tamoxifen; C038345:droloxifene