Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs.

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  • Author(s): Ieiri I;Ieiri I; Higuchi S; Sugiyama Y
  • Source:
    Expert opinion on drug metabolism & toxicology [Expert Opin Drug Metab Toxicol] 2009 Jul; Vol. 5 (7), pp. 703-29.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Informa Healthcare Country of Publication: England NLM ID: 101228422 Publication Model: Print Cited Medium: Internet ISSN: 1744-7607 (Electronic) Linking ISSN: 17425255 NLM ISO Abbreviation: Expert Opin Drug Metab Toxicol Subsets: MEDLINE
    • Publication Information:
      Publication: London : Informa Healthcare
      Original Publication: London : Ashley Publications, Ltd., c2005-
    • Subject Terms:
      Genetic Variation*/genetics; ATP-Binding Cassette Transporters/*genetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Multidrug Resistance-Associated Proteins/*genetics ; Neoplasm Proteins/*genetics ; Organic Anion Transporters/*genetics ; Organic Anion Transporters, Sodium-Independent/*genetics ; Polymorphism, Genetic/*genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Animals ; Humans ; Intestinal Absorption/genetics ; Liver/metabolism ; Liver-Specific Organic Anion Transporter 1 ; Multidrug Resistance-Associated Protein 2 ; Solute Carrier Organic Anion Transporter Family Member 1B3
    • Abstract:
      Recent pharmacogenomic/pharmacogenetic studies have disclosed important roles of drug transporters in the pharmacokinetic/pharmacodynamic (PK/PD) profiles of some clinically relevant drugs. It has concurrently been explained that variations in the drug transporter genes are associated with not only inter-individual but also inter-ethnic differences in PK/PD profiles of these drugs. This review focuses on two uptake and two efflux transporters. Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are uptake transporters, specifically expressed in the liver, and considered important for drugs, particularly as their pharmacological target organ is the liver. Two ATP-binding cassette transporters, multi-drug resistance-associated protein 2 and breast cancer resistance protein, are efflux transporters, expressed in various human tissues, and considered particularly important for intestinal drug absorption and hepatic drug elimination. All 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitors (statins) except fluvastatin are substrates for OATP1B1, but hepatobiliary (canalicular) efflux transporters differ among statins. In this review, we update the pharmacogenomic/pharmacogenetic properties of these transporters and their effects on PK/PD profiles of statins and other clinically relevant drugs. In addition, we describe a physiologically-based pharmacokinetic model for predicting the effects of changes in transporter activities on systemic and hepatic exposure to pravastatin.
    • Number of References:
      145
    • Accession Number:
      0 (ABCC2 protein, human)
      0 (ABCG2 protein, human)
      0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
      0 (ATP-Binding Cassette Transporters)
      0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (Multidrug Resistance-Associated Protein 2)
      0 (Multidrug Resistance-Associated Proteins)
      0 (Neoplasm Proteins)
      0 (Organic Anion Transporters)
      0 (Organic Anion Transporters, Sodium-Independent)
      0 (SLCO1B1 protein, human)
      0 (SLCO1B3 protein, human)
      0 (Solute Carrier Organic Anion Transporter Family Member 1B3)
    • Publication Date:
      Date Created: 20090516 Date Completed: 20100302 Latest Revision: 20211203
    • Publication Date:
      20231215
    • Accession Number:
      10.1517/17425250902976854
    • Accession Number:
      19442037