Pharmacogenetics of drug transporters.
During the last decade, a greater focus has been given to impact of genetic variation in membrane transporters on the pharmacokinetics and toxicity of numerous therapeutic drugs. While the majority of transporter-related pharmacogenetic research has been in regards to classic genes encoding the outward-directed ATP-binding cassette (ABC) transporters, such as ABCB1 (P-glycoprotein), ABCC2 (MRP2), and ABCG2 (BCRP), more studies have been conducted in recent years evaluating genes encoding solute carriers (SLC) that mediate the cellular uptake of drugs, such as SLCO1B1 (OATP1B1) and SLC22A1 (OCT1). The distribution of ABC and SLC transporters in tissues key to pharmacokinetics, such as intestine (absorption), blood-brain-barrier (distribution), liver (metabolism), and kidneys (excretion), strongly suggests that genetic variation associated with changes in protein expression or function of these transporters may have a substantial impact on systemic drug exposure and toxicity. In this current article, we will review recent advances in understanding the contribution of critical ABC and SLC transporters to interindividual pharmacokinetic and dynamic variability of substrate drugs.
Franke
R M
RM
St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, USA.
Gardner
E R
ER
Sparreboom
A
A
D002352:Carrier Proteins / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010599:Pharmacokinetics
C000715087:ABCC2 protein, human; D002352:Carrier Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D004364:Pharmaceutical Preparations