Preclinical Evaluation of [¹⁸F]LCATD as a PET Tracer to Study Drug-Drug Interactions Caused by Inhibition of Hepatic Transporters.

ABSTRACT: The bile acid analogue [¹⁸F]LCATD (LithoCholic Acid Triazole Derivative) is transported in vitro by hepatic uptake transporters such as OATP1B1 and NTCP and efflux transporter BSEP. In this in vivo "proof of principle" study, we tested if [¹⁸F]LCATD may be used to evaluate drug-drug interactions (DDIs) caused by inhibition of liver transporters. Hepatic clearance of [¹⁸F]LCATD in rats was significantly modified upon coadministration of rifamycin SV or sodium fusidate, which are known to inhibit clinically relevant uptake transporters (OATP1B1, NTCP) and canalicular hepatic transporters (BSEP) in humans. Treatment with rifamycin SV (total dose 62.5 mg·Kg^-1) reduced the maximum radioact

SUBMITTER: Testa A 

PROVIDER: S-EPMC6091370 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature