SINGLE-DOSE PHARMACOKINETICS OF ORAL FLEROXACIN IN BACTEREMIC PATIENTS

Fleroxacin is a new broad-spectrum quinolone which can be given by the oral route. The present study was designed to assess the influence of bacteremia on the pharmacokinetics of a single oral dose of fleroxaci n. Thirteen patients with proven bacteremia (one or more pairs of posi tive blood cultures, no hypotension) were given a single 400-mg flerox acin dose orally on two occasions while also receiving standard antibi otic therapy. The first dose was administered 12 to 36 h after the las t positive blood culture was drawn (day 1), and a second dose was admi nistered 7 days later (day 7 +/- 2) to compare the pharmacokinetics be tween the acute and the convalescent phases of the disease. Following each administration of fleroxacin, serial plasma samples were collecte d for up to 72 h and were analyzed for unchanged drug by a reversed ph ase high-pressure liquid chromatography technique. There were no signi ficant changes in the following pharmacokinetic parameters (mean stand ard deviation) the maximum concentration of drug in serum (6.4 +/- 1.5 versus 6.7 +/- 1.9 mg/liter), the minimum concentration of drug in se rum, defined as the concentration of drug in serum at 24 h postdose (3 .0 +/- 1.7 versus 2.5 +/- 1.2 mg/liter), the time to the maximum conce ntration of drug in serum (2.3 +/- 1.4 versus 2.0 +/- 1.2 h), and the elimination half-life (19.7 +/- 8.0 versus 17.9 +/- 6.9 h). Fleroxacin clearances were compared for each individual patient. A positive corr elation (R(2) = 0.787) was found between the values measured on day 1 and day 7. Oral clearance of fleroxacin (CL = CL/F, where F is bioavai lability) was slightly, but not significantly, reduced during the bact eremic phase (oral clearance, 43.8 +/- 23.5 versus 48.5 +/- 17.5 ml/mi n). When compared with previous results obtained in healthy young subj ects, longer times to the maximum concentration of drug in serum and e limination half-lives and higher areas under the curve were observed. This could be due to the bacteremic state, the old age of the patients (mean, 66 years), and the low renal clearance (mean calculated creati nine clearance, 71.1 ml/min). A single oral dose of 400 mg of fleroxac in provides sufficient levels in serum to cover susceptible microorgan isms for at least 24 h in bacteremic patients. Renal function appeared to be the hey element that had to be taken into consideration to adap t fleroxacin dosage profiles in our patient population. Bacteremia its elf appeared to amplify that phenomenon, but to a much lesser extent t han renal function did.