Breast Cancer Resistance Protein (BCRP) and Organic Anion Transporting Polypeptide 1B1 (OATP1B1) (BCRP/OATP1B1)

Breast Cancer Resistance Protein (BCRP, encoded by ABCG2) and Organic Anion Transporting Polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) are key membrane transporters that coordinately regulate the pharmacokinetics of rosuvastatin (PubMed: 19092647). OATP1B1 is an uptake transporter located on the basolateral (sinusoidal) membrane of hepatocytes, facilitating the entry of rosuvastatin into the liver, which is the primary site of HMG-CoA reductase inhibition (UniProt: Q9Y6L6). BCRP is an efflux transporter expressed in the apical membrane of enterocytes and the canalicular membrane of hepatocytes, where it limits intestinal absorption and promotes the biliary secretion of rosuvastatin (UniProt: Q9UNQ0). These transporters are critical for the liver-specific targeting of statins, ensuring high intrahepatic concentrations for efficacy while maintaining low systemic levels to minimize toxicity (PubMed: 15970799). Variations in the genes encoding these transporters, specifically the SLCO1B1 c.521T>C and ABCG2 c.421C>A polymorphisms, are associated with significantly increased plasma concentrations of rosuvastatin, leading to a higher risk of statin-induced myopathy and rhabdomyolysis (PubMed: 24345350). Because rosuvastatin is a sensitive substrate for both transporters, they are frequently studied together in drug-drug interaction (DDI) trials to assess the impact of inhibitors like cyclosporine or gemfibrozil on drug safety and efficacy (FDA: Drug Development and Drug Interactions). Inhibition of these pathways by concomitant medications can lead to clinically significant increases in drug exposure, necessitating dose adjustments or alternative therapies (PubMed: 21356214).

Other names

ABCG2SLCO1B1OATP-COATP2LST-1MXRABCPBCRP1Solute carrier organic anion transporter family member 1B1ATP-binding cassette sub-family G member 2Breast Cancer Resistance ProteinOrganic Anion Transporting Polypeptide 1B1

OATP1B1 facilitates the hepatic uptake of rosuvastatin from the blood, while BCRP limits its intestinal absorption and mediates its biliary efflux (PubMed: 19092647).