Tissue pharmacokinetics of fleroxacin in humans as determined by positron emission tomography.

Overview

The delivery of fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [(18)F]fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (18 mug/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2-8 h post-infusion, mug/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC(90)'s of the family Enterobacterioaceae and Neisseria gonorrhoeae are <2 mug/ml, with the great majority of the individual species 1 mug/ml, these results suggest that a single daily dose of 400 mg of fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.