Genotyping of the N-acetyltransferase2 Polymorphism in the Prediction of Adverse Drug Reactions to Isoniazid in Japanese Patients

  • HIRATSUKA Masahiro
    Department of Pharmaceutical Sciences, Tohoku University Hospital Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University
  • KISHIKAWA Yukinaga
    Department of Pharmaceutical Sciences, Tohoku University Hospital Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
  • TAKEKUMA Yoh
    Department of Pharmaceutical Sciences, Tohoku University Hospital
  • MATSUURA Masaki
    Department of Pharmaceutical Sciences, Tohoku University Hospital
  • NARAHARA Kaori
    Department of Pharmaceutical Sciences, Tohoku University Hospital
  • INOUE Tomoko
    Department of Pharmaceutical Sciences, Tohoku University Hospital
  • HAMDY Samar Ismail
    Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
  • ENDO Naomi
    Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
  • GOTO Junichi
    Department of Pharmaceutical Sciences, Tohoku University Hospital Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
  • MIZUGAKI Michinao
    Department of Pharmaceutical Sciences, Tohoku University Hospital Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University

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  To investigate the association between NAT2 genotypes and the incidence of isoniazid (INH)-induced adverse reactions, in the hope of identifying a pharmacogenetic approach that could be useful in the prediction and prevention of adverse reactions in Japanese patients, we retrospectively studied the genotypes of NAT2 in 102 Japanese patients treated with INH (without rifampicin co-administration). The subjects were classified into three groups according to their genotypes: rapid-type, intermediate-type, and slow-type. The clinical conditions of the patients were followed-up in order to evaluate the development of any adverse drug reactions (ADRs) and correlate them with patient genotypes. Six out of the 102 patients (5.9%) developed various ADRs following INH treatment. These reactions included nausea/vomiting, fever, visual impairment, and peripheral neuritis. We found a statistically significant difference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was significantly higher in the slow type than in the other two types, as 5 out of the 6 ADR patients were of the slow-type, and the other one was of the intermediate-type, while no patients of the rapid-type developed any ADRs. The results indicated that the genes coding for slow acetylation were associated with the incidence of serious ADRs following INH treatment. Our findings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.<br>

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