THE EFFECT OF INDOMETHACIN ON HEPATIC DRUG-OXIDIZING CAPACITY IN THE RAT : TRIMETHADIONE AND ANTIPYRINE METABOLISM AS AN INDICATOR

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概要

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• In this study, trimethadione (TMO) and antipyrine were chosen as model drugs to investigate the extent of hepatic drug-oxidizing capacity. It was also studied whether pretreatment of rats with indomethacin affected the formation of antipyrine metabolite. Pretreatment with indomethacin in a dose of 5 mg/kg/d for 3 d did not change the serum halflife (T_<1/2>), the total body clearance (CL), and the apparent volume of distribution (V_d) of TMO and antipyrine. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these parameters were significantly decreased as compared to controls except to V_d values in antipyrine kinetics in vivo. The contents of cytochrome P-450,and the activities of aminopyrine Ndemethylase and aniline hydroxylase were not changed by 5 mg/kg/d for 3 d of indomethacin. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these enzyme activities were significantly decreased as compared to controls. The activities of heme oxygenase were significantly increased as compared to controls in the rat treated with 5 and 8.5 mg/kg/d for 3 d of indomethacin, in vitro. The excretions of 4-hydroxyantipyrine and 3-hydroxymethyl antipyrine were not changed in the rat treated with 8.5 mg/kg for 3 d of indomethacin as compared to controls, whereas the excretion of norantipyrine was sigificantly decreased. These results, together with the previous findings, indicate that indomethacin treatment inhibited N-demethylation pathway of TMO and antipyrine metabolism.

• 社団法人日本薬学会の論文

著者

• KOBAYASHI Shinichi

  Department of Pharmacology, St. Marianna University School of Medicine

• YASUHARA Hajime

  Department of Pharmacology, School of Medicine, Showa University

• Yasuhara Hajime

  昭和大学 医学部第二薬理学教室

• Yasuhara H

  Department Of Pharmacology School Of Medicine Showa University

• Yasuhara Hajime

  Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono

• Yasuhara Hajime

  Department Of Second Pharmacology Showa University School Of Medicine

• Yasuhara H

  Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono

• OGUCHI KATSUJI

  Department of Pharmacology, School of Medicine, Showa University

• TANAKA EINOSUKE

  Department of Legal Medicine, Institute of Community Medicine

• ARAMPHONGPHAN AURATAI

  Department of Pharmacology, School of Medicine Showa University

• KURATA NORIMITSU

  Department of Biochemical Toxicology, School of Pharmaceutical Science Showa University

• KUROIWA YUKIO

  Department of Biochemical Toxicology, School of Pharmaceutical Science Showa University

• Kuroiwa Y

  Showa Univ. Tokyo Jpn

• Kuroiwa Y

  Experimental Toxicology Group Sandoz Research Laboratory

• Kuroiwa Yukio

  Department Of Biochemical Toxicology Faculty Of Pharmaceutical Sciences Showa University

• Kuroiwa Yukio

  Department Of Biochemical Toxicology School Of Pharmaceutical Science Showa University

• Oguchi K

  Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono

• Oguchi Katsuji

  Department Of Pharmacology School Of Medicine Showa University

• Kurata Norimitsu

  Department Of Pharmacology School Of Medicine Showa University

• Kurata Norimitsu

  Department Of Biochemical Toxicology School Of Pharmaceutical Science Showa University

• Kobayashi Shinichi

  Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono

• Aramphongphan Auratai

  Department Of Pharmacology School Of Medicine Showa University

• Tanaka E

  Univ. Tsukuba Ibaraki Jpn

• Takabatake E

  Department Of Toxicology Faculty Of Pharmaceutical Sciences Setsunan University

• Yasuhara Hajime

  Department Of Pharmacology School Of Medicine

• Tanaka Einosuke

  Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University

• Takabatake E

  Inst.of Commun.med

• Tanaka Einosuke

  Inst.of Commun.med

• Kobayashi Shinichi

  Department Of Biomedical Engineering Graduate School Of Medicine University Of Tokyo

• Yasuhara Hajime

  Department Of Pediatrics Yao Municipal Hospital

• Yasuhara Hajime

  Department Of Neonatal Intensive Care Unit Nara Prefectural Hospital

• Kobayashi S

  Saitama Univ. Urawa Jpn

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