Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans

Y. Yamasaki, Ichiro Ieiri, H. Kusuhara, T. Sasaki, M. Kimura, H. Tabuchi, Y. Ando, S. Irie, J. A. Ware, Y. Nakai, S. Higuchi, Y. Sugiyama

研究成果: Contribution to journalArticle査読

125 被引用数 (Scopus)

抄録

The role of breast cancer resistance protein (BCRP), an efflux ABC transporter, in the pharmacokinetics of substrate drugs in humans is unknown. We investigated the impact of genetic polymorphisms of ABCG2 (421C>A) and NAT2 on the pharmacokinetics of sulfasalazine (SASP), a dual substrate, in 37 healthy volunteers, taking 2,000 mg of conventional SASP tablets. In ABCG2, SASP AUC0-48 of C/C, C/A, and A/A subjects was 171 ± 85, 330 ± 194, and 592 ± 275 μg h/ml, respectively, with significant differences among groups. In contrast, AUC0-48 of sulfapyridine (SP) tended to be lower in subjects with the ABCG2-A allele as homozygosity. In NAT2, AUCAcSP/AUCSP was significantly higher in rapid than in intermediate and slow acetylator (SA) genotypes. We successfully described the pharmacokinetics of SASP, SP, and N -acetylsulfapyridine (AcSP) simultaneously by nonlinear mixed-effects modeling (NONMEM) analysis with regard to both gene polymorphisms. The data indicate that SASP is a candidate probe of BCRP, particularly in its role in intestinal absorption.

本文言語英語
ページ(範囲)95-103
ページ数9
ジャーナルClinical Pharmacology and Therapeutics
84
1
DOI
出版ステータス出版済み - 7 1 2008

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

フィンガープリント 「Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル