Linked Life Data

17425754

Source:http://linkedlifedata.com/resource/pubmed/id/17425754

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pubmed-article:17425754pubmed:abstractTextThe intestinal efflux pump P-glycoprotein (P-gp), the product of the multi-drug resistance-1 (MDR-1) gene, significantly influences the pharmacokinetics of several drugs. Ciclosporin is a substrate for P-gp and is metabolized by cytochrome P450 (CYP) 3A enzymes. P-gp activity is affected by several known single nucleotide polymorphisms (SNPs) and haplotypes. MDR-1 genotypes of SNPs C1236T, G2677T/A and C3435T, as well as haplotypes C-G-C and T-T-T and CYP3A5*1 genotype (predictive of CYP3A5 expression), were related to ciclosporin blood concentrations measured at both 0 and 2 h after drug dosing in 197 stable renal transplant patients. Significant differences (of a magnitude unlikely to be relevant clinically) in dose-normalized blood ciclosporin concentrations were found only between MDR-1 genotypes of the C1236T SNP and between haplotype groups C-G-C and T-T-T in patients that were expressers of CYP3A5. MDR-1 SNPs and haplotypes and also CYP3A5*1 genotype, do not appear to have a major influence on ciclosporin pharmacokinetics.lld:pubmed
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pubmed-article:17425754pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:17425754pubmed:articleTitleMulti-drug resistance gene-1 (MDR-1) haplotypes and the CYP3A5*1 genotype have no influence on ciclosporin dose requirements as assessed by C0 or C2 measurements.lld:pubmed
pubmed-article:17425754pubmed:affiliationAnalytical Unit, Cardiac & Vascular Science, St George's University of London, London, UK. frederic@sgul.ac.uklld:pubmed
pubmed-article:17425754pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17425754pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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