Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats(Biopharmacy)

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概要

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• There is an interesting clinical report indicating that aciclovir, which is mainly excreted into urine, decreases the systemic clearance of theophylline by inhibiting cytochrome P450 (CYP) 1A2-mediated metabolism. In this study, we investigated the effect of aciclovir on the metabolism of theophylline, and on the activity and expression of hepatic CYP1A2 in rats. Theophylline (10 mg/kg) was injected intravenously into rats treated with two different dosages of aciclovir. When theophylline was simultaneously administered with aciclovir (50 mg/kg), the systemic clearance of theophylline and metabolic clearance of its major metabolites, 1-methyluric acid and 1,3-dimethyluric acid, were unchanged. In place of theophylline, when 1-methyl-3-propylxanthine (2.5 mg/kg), which is almost metabolized by CYP1A2 in rats, was coadministered intravenously with aciclovir (50 mg/kg), the pharmacokinetics of 1-methyl-3-propylxanthine was also unchanged. When theophylline was administered to rats pretreated with repeated intraperitoneal injections of aciclovir (25 mg/kg twice daily for 3 d), no significant differences in the systemic clearance of theophylline and its metabolic clearance to 1-methyluric acid and 1,3-dimethy-luric acid were observed between the control and aciclovir-treated rats. This dosage of aciclovir did not change the activity of 7-ethoxyresorufin O-dealkylation, which is represented as CYP1A2 activity. In Western blot analysis, no significant change in the protein levels of hepatic CYP1A2 was observed between the control and aciclovirtreated rats. The present study suggests that aciclovir has no effect on the pharmacokinetics and metabolism of theophylline and on the activity and expression of hepatic CYP1A2 in rats.

• 公益社団法人日本薬学会の論文
• 2007-03-01

著者

• Ueyama Jun

  Department of Medical Technology, Nagoya University School of Health Sciences

• NADAI Masayuki

  Faculty of Pharmacy, Meijo University

• HASEGAWA Takaaki

  Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine

• Ueyama Jun

  Department Of Medical Technology Nagoya University School Of Health Sciences

• Ueyama Jun

  名城大学 薬学部薬剤学研究室

• Zhao Ying

  State Key Laboratory Of Biotherapy And Cancer Center West China Hospital West China Medical School S

• Zhao Ying

  Department Of Cardiology Anzhen Hospital Capital Medical University

• KIMURA Masao

  Department of Physical Electronics, Tokyo Institute of Technology

• Ueyama Jun

  Department Of Medicinal Informatics Graduate School Of Medical Science Kanazawa University ; Departm

• Nadai Masayuki

  Faculty Of Pharmacy Meijo University

• Hasegawa Takaaki

  Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine

• Hasegawa Takaaki

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• NADAI Masayuki

  Department of Pharmaceutics, Facuty of Pharmacy, Meijo University

• KATO Miki

  Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine

• YASUI Kazumasa

  Department of Pharmaceutics, Facuty of Pharmacy, Meijo University

• TSUNEKAWA Yoshimi

  Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University

• YOSHIZUMI Hideo

  Department of Pharmaceutics, Facuty of Pharmacy, Meijo University

• Kato Miki

  Department Of Food And Nutrition Japan Women's University

• Kato Miki

  Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine

• Yasui Kazumasa

  Department Of Pharmaceutics Facuty Of Pharmacy Meijo University

• Nadai Masayuki

  Department Of Pharmaceutics Faculty Of Pharmacy Meijo University

• Yoshizumi Hideo

  Department Of Pharmaceutics Facuty Of Pharmacy Meijo University

• Ueyama Jun

  Department Of Medical Technology Nagoya University School Of Health Science

• Hasegawa Takaaki

  Department Of Hospital Pharmacy Nagoya University School Of Medicine

• Zhao Ying

  State Key Laboratory Of Biotherapy And Cancer Center West China Hospital West China Medical School S

• Kimura Masao

  Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine

• Kimura Masao

  Department Of Ocean Engineering Faculty Of Marine Science And Technology Tokai University

• Tsunekawa Yoshimi

  Department Of Pharmaceutics School Of Pharmacy Aichi Gakuin University

• Kimura Masao

  Department Of Naval Architecture Faculty Of Engineering Yokohama National Univ.

• Zhao Ying

  Department of Biological Sciences and Biotechnology, Tsinghua University

• KIMURA Masao

  Department of Chemistry, Faculty of Sience, Hokkaido University

• Kimura Masao

  Department of Chemistry Nagoya University

• NADAI Masayuki

  Department of Hospital Pharmacy, Nagoya University School of Medicine

• HASEGAWA Takaaki

  Department of Bacteriology, Nagoya University School of Medicine

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