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

The bile acid analogue (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 may be used to evaluate drug-drug interactions (DDIs) caused by inhibition of liver transporters. Hepatic clearance of 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) reduced the maximum radioactivity of recorded in the liver from 14.2 ± 0.8% to 10.2 ± 0.9% and delayed by 90 seconds relative to control rats. AUC, AUC and hepatic uptake clearance CL of rifamycin SV treated rats were significantly reduced, whereas AUC was higher than in control rats. Administration of sodium fusidate (30 mg·Kg) inhibited the liver uptake of , although to a lesser extent, reducing the maximum radioactivity in the liver to 11.5 ± 0.3%. These preliminary results indicate that may be a good candidate for future applications as an investigational tracer to evaluate altered hepatobiliary excretion as a result of drug-induced inhibition of hepatic transporters.