Document Detail


Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2).
MedLine Citation:
PMID:  22123128     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent pharmacogenomic/pharmacogenetic (PGx) studies have disclosed important roles for drug transporters in the human body. Changes in the functions of drug transporters due to drug/food interactions or genetic polymorphisms, for example, are associated with large changes in pharmacokinetic (PK) profiles of substrate drugs, leading to changes in drug response and side effects. This information is extremely useful not only for drug development but also for individualized treatment. Among drug transporters, the ATP-binding cassette (ABC) transporters are expressed in most tissues in humans, and play protective roles; reducing drug absorption from the gastrointestinal tract, enhancing drug elimination into bile and urine, and impeding the entry of drugs into the central nervous system and placenta. In addition to PK/pharmacodynamic (PD) issues, ABC transporters are reported as etiologic and prognostic factors (or biomarkers) for genetic disorders. Although a consensus has not yet been reached, clinical studies have demonstrated that the PGx of ABC transporters influences the overall outcome of pharmacotherapy and contributes to the pathogenesis and progression of certain disorders. This review explains the impact of PGx in ABC transporters in terms of PK/PD, focusing on P-glycoprotein and breast cancer resistance protein (BCRP).
Authors:
Ichiro Ieiri
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Publication Detail:
Type:  Journal Article; Review     Date:  2011-11-29
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  27     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-07-16     Revised Date:  2012-08-21    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  85-105     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. ieiri-ttr@umin.ac.jp
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / chemistry,  genetics*,  metabolism*
Biological Transport
Biotransformation
Humans
Intestinal Absorption
Neoplasm Proteins / chemistry,  genetics*,  metabolism*
P-Glycoprotein / chemistry,  genetics*,  metabolism*
Pharmacokinetics*
Polymorphism, Genetic*
Protein Conformation
Tissue Distribution
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Neoplasm Proteins; 0/P-Glycoprotein

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


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