Organic anion transporting polypeptide 1B transporters (OATP1B)

Organic anion transporting polypeptide 1B (OATP1B) transporters, primarily comprising the OATP1B1 and OATP1B3 isoforms, are critical membrane proteins located on the sinusoidal (basolateral) membrane of human hepatocytes (Nakanishi & Tamai, 2012). These transporters play a fundamental role in the hepatic clearance of various endogenous substances, such as bilirubin, bile acids, and thyroid hormones, as well as a wide range of clinically significant drugs (UniProt Consortium, 2024). They are particularly well-known for mediating the hepatic uptake of HMG-CoA reductase inhibitors (statins), which is a prerequisite for their pharmacological action and subsequent metabolism (Kalliokoski & Niemi, 2009). Because OATP1B transporters are major determinants of the pharmacokinetics and systemic exposure of many drugs, they are a primary site for drug-drug interactions (DDIs). Inhibition of these transporters by drugs like cyclosporine or gemfibrozil can lead to a dramatic increase in the plasma concentration of substrate drugs, significantly increasing the risk of adverse effects such as statin-induced myopathy or rhabdomyolysis (FDA, 2020). Additionally, genetic polymorphisms in the SLCO1B1 gene, such as the 521T>C variant, are associated with reduced transporter activity and are used in clinical practice to guide statin dosing (Yee et al., 2018). Consequently, OATP1B transporters are extensively studied during drug development to ensure safety and predict potential interactions (EMA, 2012).

Other names

SLCO1B familySolute carrier organic anion transporter family member 1BOATP1B1OATP1B3OATP-COATP8OATP2LST-1LST-2SLC21A6SLC21A8

OATP1B transporters mediate the sodium-independent, facilitated uptake of amphipathic organic anions from the blood into hepatocytes; drugs typically interact as substrates for transport or as inhibitors that block the uptake of co-administered substrates (Nakanishi & Tamai, 2012).