Dataset Information

Positron Emission Tomography Imaging of [¹¹ C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A.

ABSTRACT: Using positron emission tomography imaging, we determined the hepatic concentrations and hepatobiliary transport of [¹¹ C]rosuvastatin (RSV; i.v. injection) in the absence (n = 6) and presence (n = 4 of 6) of cyclosporin A (CsA; i.v. infusion) following a therapeutic dose of unlabeled RSV (5 mg, p.o.) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux, and biliary efflux clearance (CL; mL/minute) of [¹¹ C]RSV, estimated through compartment modeling were 1,205.6 ± 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, Na⁺ -taurocholate cotransporting polypeptide, and breast cancer resistance protein inhibitor increased [¹¹ C]RSV systemic blood exposure (45%; P < 0.05), reduced its biliary efflux CL (52%; P < 0.05) and hepatic uptake (25%; P > 0.05) but did not 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 RSV.

SUBMITTER: Billington S

PROVIDER: S-EPMC6777999 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Positron Emission Tomography Imaging of [11 C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A.

Billington Sarah S Shoner Steven S Lee Scott S Clark-Snustad Kindra K Pennington Matthew M Lewis David D Muzi Mark M Rene Shirley S Lee Jean J Nguyen Tot Bui TB Kumar Vineet V Ishida Kazuya K Chen Laigao L Chu Xiaoyan X Lai Yurong Y Salphati Laurent L Hop Cornelis E C A CECA Xiao Guangqing G Liao Mingxiang M Unadkat Jashvant D JD

Clinical pharmacology and therapeutics 20190722 5

Using positron emission tomography imaging, we determined the hepatic concentrations and hepatobiliary transport of [11 C]rosuvastatin (RSV; i.v. injection) in the absence (n = 6) and presence (n = 4 of 6) of cyclosporin A (CsA; i.v. infusion) following a therapeutic dose of unlabeled RSV (5 mg, p.o.) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux, and biliary efflux clearance (CL; mL/minute) of [11 C]RSV, estimated through compartment modeling were 1 ...[more]

PMID: 31102467

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Dataset Information

Positron Emission Tomography Imaging of [¹¹ C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A.

Publications

Positron Emission Tomography Imaging of [<sup>11</sup> C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A.

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