Fig. 1.

A simplified model of Simvastatin uptake into the hepatocyte. Simvastatin is transported by the organic-anion-transporting polypeptide (OATP) into the hepatocytes, metabolized by the CYP3A4 enzymatic system, and secreted via ATP dependent membrane transport efflux proteins ABCB2 and ABCG2 that pump foreign substances out of cells. Approx. 85% of Simvastatin is cleared via hepatocytes and bile excretion, 10% through renal clearance, and 5% of total drug concentration is available (termed bioavailability). The Single nucleotide polymorphism (SNP) rs4149056 is a genetic mutation in the SLCO1B1 gene that codes for the OATP and when present results in a reduction in OATP activity, thus decreasing Simvastatin hepatocyte uptake and increasing bioavailability. Palbociclib is an antineoplastic drug used in HER2-negative, estrogen-receptor positive breast cancer, and acts as an inhibitor of the CYP3A4e enzyme