Hepatic uptake transporters

Hepatic uptake transporters are a group of membrane proteins located on the basolateral (sinusoidal) membrane of hepatocytes that facilitate the entry of endogenous compounds and xenobiotics from the blood into the liver [1, 2]. Major members include the organic anion transporting polypeptides (OATP1B1, OATP1B3, OATP2B1), the sodium-taurocholate co-transporting polypeptide (NTCP), and the organic cation transporter 1 (OCT1) [4, 6]. These transporters play a critical role in the first-pass effect and the overall hepatic clearance of many drugs, including statins, antivirals, and anti-diabetic agents [3, 10]. By mediating the uptake of substrates, they determine the intracellular concentration of drugs, which is essential for subsequent metabolism by cytochrome P450 enzymes or biliary excretion [8, 12]. Inhibition or induction of these transporters by co-administered drugs can lead to significant drug-drug interactions (DDIs), potentially causing toxicity or reduced therapeutic efficacy [11, 15]. For example, inhibition of OATP1B1 can increase the systemic exposure of statins, leading to an increased risk of myopathy [1, 10]. Furthermore, genetic polymorphisms in these transporters, such as those in the SLCO1B1 gene, are well-known to influence individual drug responses and the risk of adverse effects [3, 14]. NTCP also serves as the primary entry receptor for the Hepatitis B and D viruses, making it a direct therapeutic target for antiviral drugs like bulevirtide [4, 13]. Overall, these transporters are key determinants of drug disposition and are essential considerations in drug development and safety assessment [11, 12].

Other names

Hepatic influx transportersSinusoidal uptake transportersBasolateral uptake transportersLiver uptake transportersHepatic SLC transporters

Hepatic uptake transporters facilitate the translocation of substrates from the sinusoidal blood into hepatocytes via facilitated diffusion or secondary active transport, such as the sodium-dependent transport mediated by NTCP [1, 4]. Drugs interact with these transporters either as substrates, which are cleared from the systemic circulation into the liver for metabolism or excretion, or as inhibitors, which block the uptake of other drugs or endogenous compounds [3, 10]. This inhibition can lead to increased systemic drug concentrations and potential toxicity, or decreased hepatic concentrations and reduced efficacy [11, 12].