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• W1964647519 abstract "The long‐term oral ketoconazole (KTZ) treatment extensively inhibits hepatic CYP3A activity. We investigated the effect of the KTZ treatment on hepatic and intestinal extraction of nifedipine (NIF) using beagle dogs. Four dogs were given orally KTZ for 20 days (200 mg, bid). NIF was administered either intravenously (0.5 mg/kg) or orally (20 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. CLtot of NIF after intravenous administration decreased to about 50% during the KTZ treatment. Cmax and AUC after oral administration increased to 2.5‐fold and fourfold, respectively, by the KTZ treatment. The hepatic extraction ratio of NIF decreased to about a half by KTZ. A significant decrease in intestinal extraction ratio was not observed. In conclusion, the KTZ treatment inhibits hepatic extraction more profoundly than intestinal extraction of NIF. Therefore, inhibition of hepatic extraction of NIF by the KTZ treatment mainly results in substantial increase in systemic bioavailability in dogs. Because KTZ inhibits human CYP3A activities similar to canine CYP3A activities, the long‐term oral KTZ treatment may dramatically increase bioavailability of NIF or other CYP3A substrates in humans. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 868–873, 2002" @default.
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• W1964647519 date "2002-03-01" @default.
• W1964647519 modified "2023-10-17" @default.
• W1964647519 title "Effect of Oral Ketoconazole on First‐pass Effect of Nifedipine After Oral Administration in Dogs" @default.
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• W1964647519 doi "https://doi.org/10.1002/jps.10086" @default.
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