Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) genotypes on the serum concentrations of isoniazid and metabolites in tuberculosis patients
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概要
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For the purpose of a side-effect monitoring of isoniazid (INH), we investigated the relationship between the genotypes of drug-metabolizing enzymes involved in INH metabolism and the serum concentrations of INH and its metabolites in 129 tuberculosis patients hospitalizing in the National Hospital Organization Chiba-East Hospital. Genotype distributions of N-acetyltransferase 2 (NAT2), CYP2E1^*5B, CYP2E1^*6, Glutathione-S-transferase (GST) M1 and GST T1 were similar to those already reported in Japanese populations. Acetylating pathway of INH to acetyl isoniazid (AcINH) tended to shift to the hydrolytic pathway generating hydrazine (Hz) with the increase of mutant alleles in NAT2 gene. Serum concentration of Hz was significantly higher in slow acetylators than in rapid acetylators of NAT2. And also, serum concentration of Hz was significantly higher in the group that showed a high concentration of rifampicin (RFP) than in which RFP was not detected. The effect of CYP2E1 gene polymorphisms on the serum concentration of Hz was rarely observed, while that of GST gene polymorphism was observed in intermediate acetylators of NAT2. Hz tended to accumulate in patients with GST M1 null genotype. Therefore, it is conceivable that the risk factors of Hz accumulation are as follows: NAT2 slow acetylator phenotype, high concentration of serum RFP, and GST M1 null genotype. In these cases, we think it's necessary to pay attention to the development of hepatic disorder caused by Hz.
- 日本トキシコロジー学会の論文
- 2008-05-01
著者
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FUKINO Katsumi
Department of Geriatric Pharmacology & Therapeutics, Graduate School of Pharmaceutical Sciences, Chi
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Fukino Katsumi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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NAKAMURA Takayuki
Department of Urology, Fukushima Medical University School of Medicine
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Ueno Koichi
Department Of Drug Evaluation And Toxicological Sciences Faculty Of Pharmaceutical Sciences Chiba Un
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Sasaki Yuka
Department Of Basic Pathology National Defense Medical Collage
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Ueno Koichi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Hirai Shigekazu
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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Hashimoto Masayo
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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Yamagishi Fumio
Department of Thoracic Disease, National Hospital Organization Chiba-East National Hospital
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Hirai Shigekazu
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yamagishi Fumio
Department Of Thoracic Disease National Hospital Organization Chiba-east National Hospital
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Hashimoto Masayo
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Sasaki Yuka
Department Of Thoracic Disease National Hospital Organization Chiba-east National Hospital
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Nakamura Takayuki
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Nakamura Takayuki
Department Of Chemistry Tokyo Gakugei University
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UENO Koichi
Department of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University
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