PHARMACOKINETICS OF [F-18] TROVAFLOXACIN IN HEALTHY-HUMAN SUBJECTS STUDIED WITH POSITRON-EMISSION-TOMOGRAPHY

Tissue pharmacokinetics of trovafloxacin, a new broad-spectrum fluoroq uinolone antimicrobial agent, were measured by positron emission tomog raphy (PET) with [F-18]trovafloxacin in 16 healthy volunteers (12 men and 4 women). Each subject received a single oral dose of trovafloxaci n (200 mg) daily beginning 5 to 8 days before the PET measurements. Ap proximately 2 h after the final oral dose, the subject was positioned in the gantry of the PET camera, and 1 h later 10 to 20 mCi of [F-18]t rovafloxacin was infused intravenously over 1 to 2 min. Serial PET ima ges and blood samples were collected for 6 to 8 h, starting at the ini tiation of the infusion. Drug concentrations were expressed as the per centage of injected dose per gram, and absolute concentrations were es timated by assuming complete absorption of the final oral dose. In mos t tissues, there was rapid accumulation of the radiolabeled drug, with high levels achieved within 10 min after tracer infusion. Peak concen trations of more than five times the MIC at which 90% of the isolates are inhibited (MIC90) for most members of Enterobacteriaceae and anaer obes (> 10-fold for most organisms) were achieved in virtually all tis sues, and the concentrations remained above this level for more than 6 to 8 h. Particularly high peak concentrations (micrograms per gram; m ean +/- standard error of the mean [SEM]) were achieved in the liver ( 35.06 +/- 5.89), pancreas (32.36 +/- 20.18), kidney (27.20 +/- 10.68), lung (22.51 +/- 7.11), and spleen (21.77 +/- 11.33). Plateau concentr ations (measured at 2 to 8 h; micrograms per gram; mean +/- SEM) were 3.25 +/- 0.43 in the myocardium, 7.23 +/- 0.95 in the lung, 11.29 +/- 0.75 in the liver, 9.50 +/- 2.72 in the pancreas, 4.74 +/- 0.54 in the spleen, 1.32 +/- 0.09 in the bowel, 4.42 +/- 0.32 in the kidney, 1.51 +/- 0.15 in the bone, 2.46 +/- 0.17 in the muscle, 4.94 +/- 1.17 in t he prostate, and 3.27 +/- 0.49 in the uterus. In the brain, the concen trations (peak, similar to 2.63 +/- 1.49 mu g/g; plateau, similar to 0 .91 +/- 0.15 mu g/g) exceeded the MIC(90)s for such common causes of c entral nervous system infections as Streptococcus pneumoniae (MIC90, < 0.2 mu g/ml), Neisseria meningitidis (MIC90, <0.008 mu g/ml), and Haem ophilus influenzae (MIC90, <0.03 mu g/ml). These PET results suggest t hat trovafloxacin will be useful in the treatment of a broad range of infections at diverse anatomic sites.