Transporter-Mediated Hepatic Uptake of Ulifloxacin, an Active Metabolite of a Prodrug-Type New Quinolone Antibiotic Prulifloxacin, in Rats

Abstract

  Prulifloxacin (PUFX) is a prodrug-type new quinolone antibiotic and immediately converted to an active metabolite, ulifloxacin (UFX). It has been previously reported that UFX is highly excreted into the bile, although the hepatic uptake process of UFX has not been investigated yet. In this study, we attempted to characterize the mechanism of hepatic uptake of UFX in rats. The hepatic uptake in vivo was evaluated by integration plot analysis. Furthermore, the uptake of [¹⁴C]-UFX by isolated rat hepatocytes was measured, and the effects of several transporter inhibitors and other quinolone antibiotics on the uptake were examined. The hepatic uptake clearance of UFX (1 mg/kg) was calculated to be 37.7 mL/min/kg, which was larger than those at doses of 5 and 25 mg/kg and was decreased by co-administration of cyclosporine A (CysA; 30 mg/kg). The uptake of [¹⁴C]-UFX by isolated rat hepatocytes linearly increased up to 1 min and also inhibited by CysA. Other quinolone antibiotics inhibited the [¹⁴C]-UFX uptake in a concentration-dependent manner, whereas taurocholate and estrone-3-sulfate partially inhibited the [¹⁴C]-UFX uptake. These results demonstrate that a carrier-mediated transport system which is common to the quinolone antibiotics is involved in the uptake of UFX in the rat liver.