Pharmacokinetics of [18F]fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography

Abstract

The pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P < 0.01), while in lungs, accumulation was lower (P < 0.02). Infection of the lung or urinary tract had no effect on drug delivery to uninvolved tissues. Also, there was no difference between the results obtained at the beginning and the end of therapy. Overall, peak concentrations of drug many times the MIC at which 90% of the infecting organisms are inhibited (MIC90) were achieved in the kidneys (> 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to fleroxacin.