Polymorphic transporters and platinum pharmacodynamics

Drug Metab Pharmacokinet. 2013;28(1):19-27. doi: 10.2133/dmpk.dmpk-12-rv-073. Epub 2012 Sep 18.

Abstract

Several solute carriers and ATP-binding cassette transporters have been implicated in the influx or efflux of platinum-based chemotherapeutic agents such as cisplatin, carboplatin, and oxaliplatin. Given that many of these proteins are highly polymorphic, the genetic status of these proteins could be an important contributor to the extensive interindividual pharmacokinetic variability associated with the clinical use of these agents. In this review article, we provide an updated overview of the various transporters that have shown promise in animal models or patient populations in facilitating the movement of platinum-based agents across cell membranes, and how their function is associated with drug disposition or pharmacodynamic effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cation Transport Proteins / genetics
  • Copper Transporter 1
  • Humans
  • Membrane Transport Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / genetics
  • Organic Cation Transport Proteins / genetics
  • Platinum Compounds / pharmacokinetics*
  • Platinum Compounds / pharmacology*
  • Polymorphism, Single Nucleotide

Substances

  • ABCC4 protein, human
  • Antineoplastic Agents
  • Cation Transport Proteins
  • Copper Transporter 1
  • MATE1 protein, human
  • MATE2-K protein, human
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Organic Cation Transport Proteins
  • Platinum Compounds
  • SLC31A1 protein, human