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• W2150776007 abstract "The overall aim of this detailed investigation of the pharmacokinetics (PK) and metabolism of finasteride in pigs was to improve understanding of in vivo PK for this drug and its metabolites. Specific aims were to examine the effects of ketoconazole coadministration on the PK in three plasma compartments (the portal, hepatic, and femoral veins), bile, and urine and to use these data to study in detail the intestinal absorption and the liver extraction ratio and apply a semiphysiological based PK model to the data. The pigs received an intrajejunal dose of finasteride (0.8 mg/kg) either alone (<i>n</i> = 5) or together with ketoconazole (10 mg/kg) (<i>n</i> = 5) or an intravenous dose (0.2 mg/kg) (<i>n</i> = 3). Plasma, bile, and urine (collected from 0 to 6 h) were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry. Ketoconazole increased the bioavailability of finasteride from 0.36 ± 0.23 to 0.91 ± 0.1 (<i>p</i> < 0.05) and the terminal half-life from 1.6 ± 0.4 to 4.0 ± 1.1 h (<i>p</i> < 0.05). From deconvolution, it was found that the absorption rate from the intestine to the portal vein was rapid, and the product of the fraction absorbed and the fraction that escaped gut wall metabolism was high (f_a · F_G ∼1). Interestingly, the apparent absorption rate constant (<i>k</i>_a) to the femoral vein was lower than that to the portal vein, probably because of binding and distribution within the liver. The liver extraction ratio was time-dependent and varied with the two routes of administration. After intrajejunal administration, from 1 to 6 h, the liver extraction ratio was significantly (<i>p</i> < 0.05) reduced by ketoconazole treatment from intermediate (0.41 ± 0.21) to low (0.21 ± 0.10)." @default.
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• W2150776007 date "2011-02-11" @default.
• W2150776007 modified "2023-10-10" @default.
• W2150776007 title "In Vivo Investigation in Pigs of Intestinal Absorption, Hepatobiliary Disposition, and Metabolism of the 5α-Reductase Inhibitor Finasteride and the Effects of Coadministered Ketoconazole" @default.
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• W2150776007 doi "https://doi.org/10.1124/dmd.110.035311" @default.
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