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N-Acetyltransferase 2 Genotype-Related Efficacy of Sulfasalazine in Patients with Rheumatoid Arthritis

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Abstract

Purpose. 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.

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Author notes

  1. Tomoko Kita

    Present address: Department of Otolaryngology, Head & Neck Surgery/Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, 54, Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

  2. Shoichi Ozaki

    Present address: Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugou, Miyamae-ku, Kawasaki, 216-8511, Japan

  3. Hajime Sano

    Present address: Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, 663-8501, Japan

Authors and Affiliations

  1. Division of Clinical Pathology and Immunology, the Department of Biomedical Informatics, Graduate School of Medicine, Kobe University, 7-5-2-, Kusunoki-cho, Chuo-ku, Kobe, 750-0017, Japan

    Shunichi Kumagai & Akio Morinobu

  2. Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama, 350-0295, Japan

    Fusao Komada

  3. Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 750-0017, Japan

    Tomoko Kita & Katsuhiko Okumura

  4. Department of Clinical Immunology, Internal Medicine, Graduate School of Medicine, Kyoto University, 54, Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Shoichi Ozaki

  5. Department of Internal Medicine, National Utano Hospital, 8, Otoyama-cho, Narutaki, Nakagyo-ku, Kyoto, 616-8255, Japan

    Hiroshi Ishida

  6. Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan

    Hajime Sano

  7. Matsubara Mayflower Clinic, 4-10-16, Kano-cho, Chuo-ku, Kobe, 650-0001, Japan

    Tsukasa Matsubara

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  1. Shunichi Kumagai
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  9. Katsuhiko Okumura
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Kumagai, S., Komada, F., Kita, T. et al. N-Acetyltransferase 2 Genotype-Related Efficacy of Sulfasalazine in Patients with Rheumatoid Arthritis. Pharm Res 21, 324–329 (2004). https://doi.org/10.1023/B:PHAM.0000016246.84974.ec

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  • DOI: https://doi.org/10.1023/B:PHAM.0000016246.84974.ec

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