title: N-acetyltransferase 2 genotype-related efficacy of sulfasalazine in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  For the individual optimization of drug therapy with sulfasalazine (SASP), we studied the influence of the N-acetyltransferase 2 (NAT2) genotype on the pharmacokinetics, efficacy, and incidence of adverse reactions of SASP in patients.
  
  
  METHODS
  Ninety-six rheumatoid arthritis (RA) patients were treated or had been treated with 0.5 and/or 1.0 g/day of SASP. The wild-type allele (NAT2*4) and three variant alleles (NAT2*5B, *6A, and *7B) of NAT2 were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Plasma concentrations of SASP and its two metabolites, sulfapyridine (SP) and N-acetylsulfapyridine (AcSP), were estimated by HPLC. Therapeutic efficacy and incidence of adverse reactions were also monitored as recommended by the American College of Rheumatology.
  
  
  RESULTS
  Patients were classified into three groups by NAT2 genotyping: Rapid Type (homozygote for NAT2*4), Intermediate Type (heterozygote for NAT2*4 and variant alleles), and Slow Type (homozygote for variant alleles). There was no clear difference in the genotype frequencies between RA patients and healthy subjects. NAT2 genotypes significantly affected both the plasma concentration ratios of SP to AcSP (SP/AcSP) and the efficacy of SASP (p < 0.05). Adverse reactions to SASP were found in 26 (27.1%) out of 96 patients, and there was no difference among the three genotype groups.
  
  
  CONCLUSIONS
  NAT2 gene polymorphism is related to the plasma SP/AcSP ratio and the efficacy of SASP.
authors.affiliation: Division of Clinical Pathology and Immunology, Department of Biomedical Informatics, Graduate School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 750-0017, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
authors.forename: Fusao
authors.initials: F
authors.lastname: Komada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kita
authors.forename: Akio
authors.initials: A
authors.lastname: Morinobu
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishida
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsubara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012460:Sulfasalazine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human