Positron Emission Tomography Imaging of [11 C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A.
Clin Pharmacol Ther
; 106(5): 1056-1066, 2019 11.
Article
de En
| MEDLINE
| ID: mdl-31102467
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transport biologique
/
Ciclosporine
/
Rosuvastatine de calcium
/
Foie
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Clin Pharmacol Ther
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique