Time-Dependent Induction of Midazolam-1-hydroxylation Enzymes in Rats Treated with St. John's Wort(Biopharmacy)
スポンサーリンク
概要
- 論文の詳細を見る
Time-dependent effects of St. John's wort (SJW) on midazolam 1-hydroxylation were investigated in Wistar rats. Wistar rats treated with SJW (1000mg/kg/d) for 1, 3, and 7d were administered midazolam orally at a dose of 10mg/kg. Oral clearance of midazolam in the SJW treated rats increased time dependently, and was significant after 7d of treatment with SJW. The midazoram-1-hydroxylation activity in liver microsomes obtained from the SJW treated rats was significantly higher than in the control group. Linear correlation was observed between oral clearance and midazolam-1-hydroxylation activity in the liver microsomes, suggesting that CYP3A induction in liver mainly decreased the midazolam concentration in plasma. Immunoblotting revealed that the protein amount of CYP3A was induced within 3 d of SJW treatment. Since the midazolam-1-hydroxylation activity continuously increased for at least 7 d, the induction of CYP3A by SJW continued to cause interactions with drugs metabolized by CYP3A. It is important for persons receiving SJW for an extended time to consider its interactions with prescription drugs.
- 公益社団法人日本薬学会の論文
- 2005-08-01
著者
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YAMAMOTO Koujirou
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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HORIUCHI RYUYA
Department of Clinical Pharmacology, Gunma University Graduate School of Medicine
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Okada Yuko
Department Of Clinical Pharmacology Graduate School Of Medicine Gunma University
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Horiuchi Ryuya
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine:department
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Yamamoto Keiko
Department Of Pharmaceutics
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NAKAMURA Katsunori
Department of Clinical Pharmacology, Graduate School of Medicine, Gunma University
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Nakayama K
Laboratory Of Drug Metabolism Graduate School Of Pharmaceutical Sciences Hokkaido University
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Horiuchi Ryuya
Department Of Clinical Pharmacology Gunma University Graduate School Of Medicine
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Yamamoto Koujirou
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Yamamoto Koujirou
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine:department
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University School Of Medicine
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University Graduate School Of Medicine
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Qi Jing
Department Of Clinical Pharmacology Graduate School Of Medicine Gunma University
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Nakayama Kazuo
Laboratory Of Drug Metabolism Division Of Pharmacobio-dynamics Graduate School Of Pharmaceutical Sci
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HOSOKAWA Shin
Department of Pharmacy, The Gunma University Hospital, Gunma University School of Medicine
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Nakayama Katsuo
Department Of Clinical Pharmacology Graduate School Of Medicine Gunma University
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Horiuchi Ryuya
Department Of Clinical Pharmacology And Department Of Pharmacy Gunma University School Of Medicine
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Nakamura Katsunori
Department Of Clinical Pharmacology Graduate School Of Medicine Gunma University
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Hosokawa Shin
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine
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Yamano Katsuhiro
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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