title: 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 [(14)C]-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 [(14)C]-UFX by isolated rat hepatocytes linearly increased up to 1 min and also inhibited by CysA. Other quinolone antibiotics inhibited the [(14)C]-UFX uptake in a concentration-dependent manner, whereas taurocholate and estrone-3-sulfate partially inhibited the [(14)C]-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.
authors.affiliation: Toxicology and Pharmacokinetics Research Labs, Pharmaceutical Research Center, Meiji Seika Kaisha LTD, Yokohama, Japan. yukihiro_yagi@meiji.co.jp
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yagi
authors.forename: Makoto
authors.initials: M
authors.lastname: Aoki
authors.forename: Maki
authors.initials: M
authors.lastname: Iguchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001692:Biological Transport; D001711:Biotransformation; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004148:Dioxolanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004148:Dioxolanes; D024841:Fluoroquinolones; D049990:Membrane Transport Modulators; D010879:Piperazines; D011355:Prodrugs; D015363:Quinolones; C074190:ulifloxacin; C074191:prulifloxacin