Document Detail


MDR1 genotype-related pharmacokinetics: fact or fiction?
MedLine Citation:
PMID:  16415525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multidrug resistant transporter MDR1/P-glycoprotein, the gene product of MDR1, is a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette superfamily of membrane transporters. A number of various types of structurally unrelated drugs are substrates for MDR1, and MDR1 and other transporters are recognized as an important class of proteins for regulating pharmacokinetics. The first investigation of the effects of MDR1 genotypes on pharmacotherapy was reported in 2000; a silent single nucleotide polymorphism (SNP), C3435T in exon 26, was found to be associated with the duodenal expression of MDR1, and thereby the plasma concentration of digoxin after oral administration. In the last 5 years, clinical studies have been conducted around the world on the association of MDR1 genotype with MDR1 expression and function in tissues, and with the pharmacokinetics and pharmacodynamics of drugs; however, there are still discrepancies in the results on C3435T. In 1995, a novel concept to predict in vivo oral pharmacokinetic performance from data on in vivo permeability and in vitro solubility has been proposed, and this Biopharmaceutical Classification System strongly suggested that the effects of intestinal MDR1 on the intestinal absorption of substrates is minimal in the case of commercially available oral drugs, and therefore MDR1 genotypes are little associated with the pharmacokinetics after oral administration. This review summarizes the latest reports for the future individualization of pharmacotherapy based on MDR1 genotyping, and attempts to explain discrepancies.
Authors:
Toshiyuki Sakaeda
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  20     ISSN:  1347-4367     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2006-01-17     Completed Date:  2006-02-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  391-414     Citation Subset:  IM    
Affiliation:
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan. sakaedat@med.kobe-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Area Under Curve
Genes, MDR / genetics*
Genotype
Humans
Pharmaceutical Preparations / administration & dosage,  metabolism
Pharmacokinetics*
Polymorphism, Genetic / genetics
RNA, Messenger / biosynthesis
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations; 0/RNA, Messenger

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


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