Pharmacokinetics and biliary elimination of temafloxacin in pigs

The purpose of the present work was to investigate the 48 h pharmacokinetic and biliary elimination of temafloxacin, administered intraduodenally at a single dose of 10 mg/kg to six conscious pigs provided with a double terminal choledocal fistula allowing the collection and the reinstillation of bile. The concentrations of temafloxacin in biological fluids were measured by both HPLC and bioassay. The mean serum half-life of temafloxacin was 11.45 +/- 4.4 h and the apparent oral clearance (assuming a 95% bioavailability) was 171 +/- 66 mL/min. The penetration of temafloxacin into bile is significant as indicated by a bile/serum AUC ratio of 9.1 +/- 2.2. The 0-45 h biliary excretion amounted to 2.002 +/- 0.8 mg, representing 0.9 +/- 0.3% of the administered dose. Biliary peak concentrations ranged from 8.0 to 37.5 mg/L and the 24 h mean biliary concentration was 3.7 +/- 2.4 mg/L. No statistically significant differences between HPLC and bioassay concentrations or AUCs could be observed in bile, indicating that temafloxacin is not extensively biotransformed into active metabolites in this model. These data, together with data in man, suggest that temafloxacin could be a useful agent for the treatment of biliary tract infections.