BILIARY-EXCRETION OF RUFLOXACIN IN HUMANS

Rufloxacin is a new once-daily antibacterial fluoroquinolone with a lo ng half-life. The aim of the present study was to evaluate the plasma and biliary kinetics and biliary and urinary excretion of rufloxacin i n patients with extrahepatic cholestasis. Twelve patients with total e xternal percutaneous transhepatic biliary drainage; were given a singl e oral dose of 400 mg of rufloxacin. Plasma, bile, and urine samples a nd fractions were collected over 72 h after drug administration. Ruflo xacin and its major metabolite, the N-desmethyl derivative, were measu red by high-performance liquid chromatography. Maximum rufloxacin conc entrations in plasma and bile (means +/- standard deviations) were 4.0 5 +/- 1.38 mu g/ml and 8.24 +/- 7.16 mu g/ml, respectively, and were r eached in 4.2 +/- 3.0 h and 4.2 +/- 3.5 h, respectively. The terminal elimination half-life of rufloxacin in plasma was 45.1 +/- 13.5 h. App arent plasma clearance was 31.3 +/- 10.5 ml/min, while biliary clearan ce was 0.4 +/- 0.2 ml/min and renal clearance was 12.7 +/- 6.0 ml/min. In 72 h, 0.9% +/- 0.8% of the dose given was recovered in bile and 27 .2% +/- 12.0% was recovered in urine. Biliary concentrations exceeded the MICs of most common biliary tract pathogens for at least 24 h afte r administration. The broad antibacterial spectrum of rufloxacin and i ts high and prolonged biliary concentrations suggest that this drug ma y be useful for treatment of biliary tract infections.