Membrane transporters are now recognized as important determinants of the transmembrane passage of drugs. Organic
anion transporting
polypeptides (OATP) form a family of influx transporters expressed in various tissues important for pharmacokinetics. Of the 11 human
OATP transporters, OATP1B1, OATP1B3 and OATP2B1 are expressed on the sinusoidal membrane of hepatocytes and can facilitate the liver uptake of their substrate drugs. OATP1A2 is expressed on the
luminal membrane of small intestinal enterocytes and at the blood-brain barrier, potentially mediating
drug transport at these sites. Several clinically used drugs have been identified as substrates of
OATP transporters (e.g. many
statins are substrates of OATP1B1). Some drugs may inhibit
OATP transporters (e.g.
cyclosporine) causing pharmacokinetic
drug-drug interactions. Moreover, genetic variability in genes encoding
OATP transporters can result in marked inter-individual differences in pharmacokinetics. For example, a single nucleotide polymorphism (c.521T > C, p.Val174Ala) in the SLCO1B1 gene encoding OATP1B1 decreases the ability of OATP1B1 to transport active
simvastatin acid from portal circulation into the liver, resulting in markedly increased plasma concentrations of
simvastatin acid and an enhanced risk of
simvastatin-induced
myopathy. SLCO1B1 polymorphism also affects the pharmacokinetics of many other, but not all (
fluvastatin),
statins and that of the
antidiabetic drug repaglinide, the
antihistamine fexofenadine and the
endothelin A receptor antagonist
atrasentan. This review compiles the current knowledge about the expression and function of human
OATP transporters, their substrate and inhibitor specificities, as well as pharmacogenetics.