N-Acetyltransferase2 Genotype Correlated with Isoniazid Acetylation in Japanese Tuberculous Patients
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概要
- 論文の詳細を見る
Isoniazid(INH) is metabolized by polymorphic N-acetyltransferase2(NAT2). In the present study, the relationship between the NAT2 genotype and the INH acetylator phenotype was examined in Japanese tuberculous patients and compared with healthy subjects. Subjects were classified according to the genotyping into NAT2^* 5B(allele4), NAT2^* 6A(allele3) and NAT2^* 7B(allele2), using the PCR-RFLP method. Twelve healthy subjects and 7 tuberculous patients participated in the INH acetylator phenotyping study, in which each subject was administered an oral dose of INH, followed by urine sampling for 24h. Urinary concentrations of INH and N-acetylisoniazid(AcINH) were measured by the HPLC method. The urinary recoveries of INH(% of dose) in healthy subjects in relation to NAT2 genotyping were as follows : 6.4±2.2 in the homozygotes for the wild-type allele, 10.7±2.2 in the compound heterozygotes for the mutant allele, and 38.6±6.4 in the homozygotes for the mutant allele. In the patients study, the findings in the corresponding three groups were 4.0±1.7, 8.8 and 18.3±9.3. Although no significant difference was found because of the lower systemic exposure of INH in patients compared with healthy subjects, there were differences in the disposition kinetics of INH between subjects with and without mutations in the NAT2 gene, and these findings were observed not only in healthy subjects but also in patients who had comedicated drugs and hepatic dysfunctions. The findings indicated that the metabolism of INH by NAT2 is clearly impaired in subjects with mutations in the NAT2 gene, and thus genotyping for three NAT2 point mutations was adequate to predict the metabolism of INH in Japanese tuberculous patients as well as healthy subjects. This NAT2 genotyping could become a useful alternative to TDM for INH.
- 公益社団法人日本薬学会の論文
- 2001-05-01
著者
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TANIGAWARA Yusuke
Department of Pharmacy, School of Medicine, Keio University
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Nakamura T
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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OKUMURA Katsuhiko
Department of Hospital Pharmacy, Kobe University School of Medicine
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SAKAEDA Toshiyuki
Department of Hospital Pharmacy, Kobe University School of Medicine
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Kimura T
Kobe University Graduate School Of Medicine
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KITA Tomoko
Department of Hospital Pharmacy, School of Medicine, Kobe University
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IWAKAWA Seigo
Kobe Pharmaceutical University
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Okumura K
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Takara Kohji
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Takara Kohji
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Sakaeda Toshiyuki
Department Of Hospital Pharmacy Kobe University Hospital
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Chikazawa Shinji
Department of Endocrinology and Metabolism, Hirosaki University Graduated School of Medicine
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IWAKAWA Seigo
Department of Pharmaceutics, Kobe Pharmaceutical University
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KOMADA Fusao
Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University
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Kita T
Institute Of Natural Science Kobe University
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Shirakawa T
Kobe University School Of Medicine
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Kamiyama Fumio
京都大学再生医科学研究所
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Kodama Fusao
Cosmed Pharmaceutical Co. Ltd.
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Iwakawa S
Department Of Cardiology Miki
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Iwakawa Seigo
Department Of Hospital Pharmacy School Of Medicine Kobe University : Department Of Pharmacy Kyoto Un
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Tanigawara Yusuke
Department Of Clinical Pharmacokinetics And Pharmacodynamics School Of Medicine Keio University
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Kita Tomoko
Department Of Applied Physics Osaka University
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Okumura Katsuhiko
Department Of Hospital Pharmacy School Of Medicine Kobe University
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HATANAKA Hisakatsu
Hyogo Prefectural Institute of Public Health
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Okumura Katsuhiko
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Okumura Katsuhiko
Department Of Hospital Pharmacy Kyoto Pharmaceutical University:department Of Hospital Pharmacy Kobe
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Hatanaka Hisakatsu
Hyogo Prefrctural Institute Of Public Health
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Komada F
Department Of Pharmacy Kobe University School Of Medicine
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Shinobu Ichikawa
Department Of Cardiology Miki
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Nakamura Takeshi
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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Sakai T
Department Of Internal Medicine And Gastrointestinal Endoscopy Saga Medical School
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Chikazawa Shinji
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Chikazawa Shinji
Department Of Endocrinology And Metabolism Hirosaki University Graduated School Of Medicine
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Koishi Tomokazu
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Ichikawa Shinobu
Department Of Cardiology Miki City Hospital
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Iwakawa Seigo
Department of Cardiology, Miki
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