OATP1A2, OAT1, and OAT3

Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant?

“…Of these, OATP1B1 ( SLCO1B1 ), OATP1B3 ( SLCO1B3 ), and OATP2B1 ( SLCO2B1 ) are largely expressed at the sinusoidal endothelium of the liver and mediate hepatocellular uptake of substrates from portal circulation; OATP2B1 is also expressed on intestinal endothelia, where it facilitates the absorption of its substrates . Interestingly, OATP1A2 ( SLCO1A2 ) is expressed in the distal nephron, apical membrane of cholangiocytes, ciliary body epithelium of the eye, and capillary endothelia of the brain and is now thought to facilitate brain entry of certain medications . Select OATP variants and their effects are summarized in Table .…”

“…Our group had demonstrated decreased transport of δ‐opioid receptor agonists (deltorphin II and [ d ‐penicillamine‐2,5]‐enkephalin, DPDE) in HeLa cells expressing the SLCO1A2 variant c.516A>C (rs11568563) . SLCO1A2 c.516A>C has an allele frequency of approximately 2% and 5% to 7% in African and white individuals, respectively, and appears to cause a reduction in cell surface transporter expression . The effects of SLCO1A2 c.516A>C have also been investigated in relation to imatinib (a tyrosine kinase inhibitor) pharmacokinetics.…”

“…There have been a number of excellent publications in the past 5 years, in terms of in vitro as well as in vivo guidance for transporter‐related studies during drug discovery and development . Shown below is a very brief 6‐step summary of what should be viewed as our opinion, with regard to drug transporters and clinically relevant polymorphisms.…”