Effect of Chronic Administration of Ritonavir on Function of Cytochrome P450 3A and P-Glycoprotein in Rats(Biopharmacy)
スポンサーリンク
概要
- 論文の詳細を見る
Ritonavir (RTV) is well known as an inhibitor of many drugs that are metabolized by cytochrome P450 (CYP) 3A or fluxed via P-glycoprotein (Pgp), although it is also reported that RTV is a potent inducer for them. In this study, to elucidate these contradictory phenomena, functional changes of CYP3A or Pgp during chronic administration of RTV were examined in rats. After pretreatment with RTV for indicated days (day 3-day 14), rats were used in the experiments. The area under the plasma drug concentration vs. time curve (AUC_<0-∞> after oral administration of RTV (20 mg/kg) to these rats showed an RTV-treatment period-dependent decrease, and the mean AUC_<0-∞> of RTV in Day 14 rats decreased significantly by 57% as compared to the control. The AUC_<0-∞> after intravenous (i. v.) administration of RTV to Day 3 and Day 5 rats increased significantly by 28% and 22%, respectively, while there were no significant changes in the AUC_<0-∞> in Day 7 and Day 14 rats as compared to the control. As for i. v. administration of erythromycin (EM) or midazolam (MDZ) to RTV-treated rats, the AUC_<0-∞> in Day 3 and Day 5 rats increased significantly as compared to the control, while in Day 7 rats and rifampicintreated rats, the AUC_<0-∞> of EM decreased significantly by 82% and 42%, respectively, as compared to the control. For MDZ, there were no significant changes in the AUC_<0-∞> in Day 7 or Day 14 rats. After i. v. administration of rhodamine123 (Rho123), the excretion clearances from blood circulation to the intestinal lumen and the biliary excretion clearances in Day 14 rats increased markedly by 2.2-fold and 2.6-fold as compared to the control. It has been confirmed that RTV is not only a potent inhibitor but also a potent inducer of CYP3A, and that RTV is a potent inducer of intestinal Pgp. This property of RTV is responsible for regulating the oral bioavailability of drugs that are mediated by CYP3A and Pgp.
- 公益社団法人日本薬学会の論文
- 2005-01-01
著者
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TAKADA Kanji
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Takada Kanji
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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Takada K
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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TERASAKA Shuichi
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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ITO Yukako
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Takada Kanji
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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Terasaka Shuichi
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Sugioka Nobuyuki
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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KAGEYAMA Michiharu
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Kageyama M
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Takada K
Kyoto Pharmaceutical Univ. Kyoto Jpn
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NAMIKI Hitomi
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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TOGAWA Tatsuya
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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FUKUSHIMA Hiroto
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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TANAKA Akina
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Tanaka Akina
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Togawa T
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Shibata Nobuhito
Dep. Of Pharmacokinetics Kyoto Pharmaceutical Univ.
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Namiki Hitomi
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Fukushima Hiroto
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Inoue Yuji
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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ITO Yukako
Department of Dermatology and Plastic Surgery, Head & Neck Surgery
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