Long-lasting enhancement of CYP activity after discontinuation of repeated administration of phenobarbital in dogs |
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| Authors: | K Fukunaga M Saito E Matsuo M Muto K Mishima M Fujiwara K Orito |
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| Institution: | aDepartment of Pharmacology, School of Veterinary Medicine, Azabu University, 1–17–71 Fuchinobe, Sagamihara, Kanagawa 229–8501, Japan;bDepartment of Surgery II, School of Veterinary Medicine, Azabu University, 1–17–71 Fuchinobe, Sagamihara, Kanagawa 229–8501, Japan;cDepartment of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8–19–1 Nanakuma, Jyonan, Fukuoka, Fukuoka 814–0180, Japan |
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| Abstract: | We investigated how long in vivo hepatic cytochrome P450 (CYP) activity is enhanced even after discontinuation of repeated oral administration of phenobarbital (PB) in dogs using antipyrine clearance, which reflects hepatic CYP activity. A single antipyrine (5 mg/kg) was administered intravenously before and 34 days after the repeated oral administration of PB (5 mg/kg, bid) and 2, 4, 6, and 8 weeks after the discontinuation of PB in 5 dogs. Antipyrine clearance was increased by the repeated administration of PB, and remained increased 2 and 4, but not 6 and 8 weeks after the discontinuation of PB. The result suggests that hepatic CYP activity was enhanced by the repeated administration of PB, and this enhancement may last for at least 4 weeks even after its discontinuation. |
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| Keywords: | Antipyrine Pharmacokinetics Enzyme induction Cytochrome P450 Phenobarbital Dog |
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