Participation of P450-Dependent Oxidation of Isoniazid in Isonicotinic Acid Formation in Rat Liver

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概要

• 論文の詳細を見る

• By determining the formation amount of isonicotinic acid (INA) from isonicotinic acid hydrazide (isoniazid : INH) in isolated rat hepatocytes, we were able to identify the involvement of the oxidative cleavage of the acid hydrazide. INA formation from INH increased significantly using the isolated hepatocytes prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), dexamethazone (DEX) and rifampicin (RIF), respecitively, in comparison to the control group. On the other hand, a remarkable decrease in INA formation from INH was observed by the addition of such P450 inhibitor as metyrapone or cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to the isolated hepatocytes prepared from PB-pretreated rats. By further experiments using rat hepatic microsomes, the oxidative pathway of INA formation in INH metabolism was determined to be P450-dependent, since NADPH and oxygen were both essential for the oxidative pathway of INH to INA and the amount of INA formation was also significantly increased by P450 inducers. Regarding acetylisoniazid (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was little observed in the microsomal experiments.

• 公益社団法人日本薬学会の論文
• 1998-04-15

著者

• NODA Hiroshi

  Department of Legal Medicine, Kinki University School of Medicine

• Yoshitani Takashi

  Faculty Of Pharmaceutical Sciences Kyushu University

• ONO Yoko

  Faculty of Pharmaceutical Sciences, Kyushu University

• WU Xiuzhong

  Faculty of Pharmaceutical Sciences, Kyushu University

• NODA Atsuko

  Faculty of Pharmaceutical Sciences, Kyushu University

• Ono Y

  Chugai Pharmaceutical Co. Ltd. Tokyo Jpn

• Ono Yoko

  Faculty Of Agriculture Shinshu University

• Noda Hiroshi

  Department Of Animal Health Faculty Of Veterinary Medicine Rakuno Gakuen University

• Wu Xiuzhong

  Faculty Of Pharmaceutical Sciences Kyushu University

• Noda Atsuko

  Faculty Of Pharmaceutical Sciences Kyushu University

• Noda H

  Faculty Of Pharmaceutical Sciences Kyushu University

• Noda H

  Univ. Tsukuba

• Noda A

  Faculty Of Pharmaceutical Sciences Kyushu University

• WU Xiuzohng

  Faculty of Pharmaceutical Sciences, Kyushu University

• Noda Hiroshi

  Department Of Hospital Pharmacy School Of Medicine University Of Occupational And Environmental Heal

• Noda A

  Faculty Of Pharmaceutical Sciences Kyushu University School Of Medicine Kyushu University:department

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