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

Masahiro Hiratsuka, Yoh Takekuma, Masaki Matsuura, Kaori Narahara, Tomoko Inoue, Samar Hamdy Ismail, Naomi Endo

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62 Citations (Scopus)

Abstract

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 classiôed 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 (5.9z) developed various ADRs following INH treatment. These reactions included nauseaWvomiting, fever, visual impairment, and peripheral neuritis. We found a statistically signi ôcant diference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was signi ôcantly 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 ôndings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalDrug metabolism and pharmacokinetics
Volume17
Issue number4
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • NAT2
  • adverse drug reaction
  • genetic polymorphism
  • isoniazid
  • pharmacogenetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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