Document Detail


Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans.
MedLine Citation:
PMID:  18167504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 AUC(0-48) of C/C, C/A, and A/A subjects was 171 +/- 85, 330 +/- 194, and 592 +/- 275 microg h/ml, respectively, with significant differences among groups. In contrast, AUC(0-48) of sulfapyridine (SP) tended to be lower in subjects with the ABCG2-A allele as homozygosity. In NAT2, AUC(AcSP)/AUC(SP) 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.
Authors:
Y Yamasaki; I Ieiri; H Kusuhara; T Sasaki; M Kimura; H Tabuchi; Y Ando; S Irie; Ja Ware; Y Nakai; S Higuchi; Y Sugiyama
Related Documents :
8764834 - A possible involvement of melanocortin 1-receptor in regulating feather color pigmentat...
8872464 - Founder effect in spinal and bulbar muscular atrophy (sbma).
19556784 - Extrachromosomal circular dna in eukaryotes: possible involvement in the plasticity of ...
25489864 - Quick fluorescent in situ hybridization protocol for xist rna combined with immunofluor...
20932954 - Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hi...
1648374 - Congenital spherocytosis, b19 parvovirus infection and inherited interstitial deletion ...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-02
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  84     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-19     Completed Date:  2008-07-07     Revised Date:  2010-09-08    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  95-103     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics*,  metabolism
Adult
Arylamine N-Acetyltransferase / genetics*,  metabolism
Humans
Male
Neoplasm Proteins / genetics*,  metabolism
Pharmacogenetics
Polymorphism, Genetic / drug effects,  genetics*
Sulfasalazine / blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Neoplasm Proteins; 599-79-1/Sulfasalazine; EC 2.3.1.5/Arylamine N-Acetyltransferase; EC 2.3.1.5/NAT2 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The role of molecular imaging in drug discovery and development.
Next Document:  US Food and Drug Administration's Total Diet Study: dietary intake of perchlorate and iodine.