Abstract
Transporter proteins, in particular P-glycoprotein (Pgp), are important determinants in absorption, tissue targeting, and elimination of drugs. In addition to physiological and environmental factors, its expression and function are modified by genetic polymorphisms of the MDR1 gene. So far, several MDR1 SNPs have been identified, and mutations at positions 2677 and 3435 were associated with alteration of Pgp expression and/or function. In contrast to drug-metabolizing enzymes (eg, CYP2D6), for which loss of function mutations or gene amplification manifests as distinct phenotypes in the population, the impact of MDR1 polymorphisms on pharmacokinetics and pharmacodynamics of Pgp substrates is moderate. Clinical studies on the effects of the C3435T polymorphism and drug treatment with cardiac glycosides, the immunosuppressants cyclosporine and tacrolimus, HIV protease inhibitors, and tricyclic antidepressants are discussed.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
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Abnormalities, Drug-Induced / genetics
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Abnormalities, Drug-Induced / metabolism
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Animals
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Antidepressive Agents, Tricyclic / metabolism
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Antidepressive Agents, Tricyclic / pharmacology
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Cardiac Glycosides / metabolism
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Cardiac Glycosides / pharmacokinetics
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Cardiac Glycosides / pharmacology
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Genes, MDR / genetics*
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HIV Protease Inhibitors / metabolism
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HIV Protease Inhibitors / pharmacology
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Humans
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Immunosuppressive Agents / adverse effects
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacology
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Mutation
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Polymorphism, Genetic*
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Polymorphism, Single Nucleotide
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antidepressive Agents, Tricyclic
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Cardiac Glycosides
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HIV Protease Inhibitors
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Immunosuppressive Agents