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OATP1B1Organic Anion Transport Proteins 1b1 (transporter)
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Another key metabolic step with statins is hepatic uptake with OATPs, especially OATP1B1. (12) All statins are substrates for OATP1B1 (figure).
Although in vitro assays were performed in cells expressing human OATP1B1, we chose the rat model for our investigations as the human and the rat orthologs of OATP1B1 exhibit very similar transport characteristics.
OATP1B1 is also suppressed by an FXR-dependent pathway during cholestasis.
The best-studied genetic contributor to statin-induced side effects is SLCO1B1 (also referred to as SLC21A6, OATP-C, or OATP1B1), which codes for a hepatic drug transporter that mediates the hepatic uptake of statins.
Funk, "Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3," Drug Metabolism & Disposition, vol.
However, OCT1 and OATP1B1 are both found to have clinically relevant polymorphisms.
The human organic anion transporting polypeptide 1B1 (OATP1B1) (gene symbol SLCO1B1, previously OaTP2, OATP-C, and LST-1) [4] is expressed solely on the basolateral membrane of hepatocytes, facilitating the uptake of clinically relevant compounds such as antibacterial drugs, statins, and chemotherapeutic drugs [5].
The seven are P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3), organic cation transporter 2 (OM), and organic anion transporters 1 and 3 (OAT1 and OAT3).
The transporters recommended for initial assessment generally Included those for which A clinical relevance to drug disposition has Been identified, namely, the efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), and the uptake transporters OCT2, OAT1, OAT3, OATP1B1 and OATP1B3.
Because of the structure and size of MCs, active uptake into cells occurs via organic anion-transporting polypeptides (OATP/Oatp), as confirmed for liver-specific human OATP1B1 and OATP1B3, mouse Oatp1b2 (mOatp 1b2), skate Oatp 1d1, and the more widely distributed OATP1A2 expressed, for example, at the blood--brain barrier.