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• W2132859347 abstract "Bazedoxifene is a selective estrogen receptor modulator under development for the prevention and treatment of osteoporosis. The disposition of [¹⁴C]bazedoxifene was determined in six healthy postmenopausal women after administration of a single oral dose of 20 mg (200 μCi). After dosing, blood was collected at frequent intervals, and urine and fecal samples were collected for up to 10 days. Aliquots of plasma, blood, urine, and fecal homogenates were analyzed for concentrations of radioactivity. Bazedoxifene metabolite profiles in plasma and feces were determined by high-performance liquid chromatography with radioactivity flow detection; metabolite structures were confirmed by liquid chromatography-mass spectrometry. Bazedoxifene was rapidly absorbed, exhibiting a mean peak plasma concentration of 3.43 ng/ml at 1.2 h postdose. The total mean recovery of the radioactive dose in excreta was 85.6%, with the majority recovered in feces (84.7%) and only a small fraction (0.81%) in urine. Radiochromatograms of plasma revealed that glucuronidation was the major metabolic pathway; little or no cytochrome P450-mediated metabolism was evident. The majority of circulating radioactivity was constituted by metabolites, with bazedoxifene-5-glucuronide being the predominant metabolite (up to 95%). Bazedoxifene-4′-glucuronide was a minor metabolite (up to 20%), and unchanged bazedoxifene represented 0 to 13% of the radioactivity in most plasma samples. Unchanged bazedoxifene was the major radioactive component in feces, however, reflecting unabsorbed drug and/or glucuronides that were hydrolyzed by intestinal bacterial enzymes. [¹⁴C]Bazedoxifene was generally well tolerated. These findings demonstrated that, after oral administration in healthy postmenopausal women, bazedoxifene was rapidly absorbed, metabolized via glucuronidation, and excreted predominantly in feces." @default.
• W2132859347 created "2016-06-24" @default.
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• W2132859347 date "2009-03-09" @default.
• W2132859347 modified "2023-09-25" @default.
• W2132859347 title "Metabolic Disposition of [¹⁴C]Bazedoxifene in Healthy Postmenopausal Women" @default.
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• W2132859347 doi "https://doi.org/10.1124/dmd.108.023861" @default.
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