N-Acetyltransferase 2 Genotype Correlates with Sulfasarazine Pharmacokinetics after Multiple Dosing in Healthy Japanese Subjects
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概要
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Sulfapyridine(SP)is metabolized by polymorphic N-acetyltransferase 2(NAT2)[EC 2.3.1.5]. In this study, the correlation between the NAT2 genotype and the pharmacokinetics of SP after multiple oral dosing of sulfasalazine(SASP)was examined to elucidate the effect of multiple dosing on the predictability of the phenotype by NAT2 genotyping. Seven healthy subjects were classified into two groups; the homozygotes for the wild-type allele, NAT2^*4/^*4(Group I)and the compound heterozygotes for the mutant allele(NAT2*4/*6A or NAT2^*4/^*7B)(Group II). All received once-daily 1 g of SASP(Salazopyrin[◯!R]orally for 8d. Plasma concentrations and urinary recoveries of SASP, SP and N-acetylsulfapyridine(AcSP)were monitored for 8d. At 24h on Day 1, the plasma concentration of SASP was lower and those of SP and AcSP were higher in Group II compared with Group I, but there was no significant difference. The plasma concentration ratio of AcSP to SP(AcSP/SP)tended to be lower in Group II. Urinary recoveries of SP and AcSP were increased in Group II, and their ratio was slightly reduced in Group II. Multiple dosing for 8d resulted in an increase in the plasma concentrations of SASP, SP and AcSP. The difference between Group I and II was marked compared with single dosing, resulting in a significant difference in the plasma concentration of SP and the ratio of AcSP/SP. The simple input-output pharmacokinetic model applied for the analysis of plasma concentrations and urinary recoveries of SP and AcSP suggested the acetylation of SP into AcSP was 2.7-fold reduced in Group II(p=0.064).
- 公益社団法人日本薬学会の論文
- 2001-10-01
著者
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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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Kasuga Masato
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Kakumoto M
Department Of Hospital Pharmacy School Of Medicine Kobe University
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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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Okumura K
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Aoyama Nobuo
Department Of Endoscopy School Of Medicine Kobe University
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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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Kita T
Institute Of Natural Science Kobe University
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Shirakawa T
Kobe University School Of Medicine
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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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ADACHI Shin-ichi
Department of Hospital Pharmacy, School of Medicine, Kobe University
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SAKAI Toshiyuki
2nd Department of Internal Medicine, School of Medicine, Kobe University
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AOYAMA Nobuo
2nd Department of Internal Medicine, School of Medicine, Kobe University
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KASUGA Masato
2nd Department of Internal Medicine, School of Medicine, Kobe University
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Adachi Shin-ichi
Department Of Hospital Pharmacy School Of Medicine Kobe University
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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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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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Aoyama Nobuo
Second Department Of Internal Medicine Kobe University School Of Medicine
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Koishi Tomokazu
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Kaneko M
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Chiba Institute Of Science
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Kaneko Masayuki
千葉科学大学
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