PET Imaging of [ 11 C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporine A

Using positron emission tomography (PET) imaging, we determined the hepatic concentrations and hepatobiliary transport of [11C]rosuvastatin (IV injection) in the absence (n=6) and presence (n=4 of 6) of cyclosporine A (CsA, IV infusion) following a therapeutic dose of unlabeled rosuvastatin (RSV) (5 mg, PO) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux and biliary efflux clearance (mL/min) of [11C]rosuvastatin, estimated through compartment modeling were 1205.6±384.8, 16.2±11.2 and 5.1±1.8, respectively (n=6). CsA (blood concentration: 2.77±0.24 μM), an organic-anion-transporting polypeptide (OATP), Na+-taurocholate cotransporting polypeptide (NTCP) and breast cancer resistance protein (BCRP) inhibitor increased [11C]rosuvastatin systemic blood exposure (45%; p 0.05) but didn’t affect its distribution into the kidneys. CsA increased plasma concentrations of coproporphyrin I and III and total bilirubin by 297±69%, 384±102% and 81±39%, respectively (p<0.05). These data can be used in the future to verify predictions of hepatic concentrations and hepatobiliary transport of rosuvastatin.