Pharmacokinetics of Fleroxacin as Studied by Positron Emission Tomography and [18F]Fleroxacin

A new method of tracing the disposition of fleroxacin was tested in infected and noninfected animals in an effort to develop a technique that might be applicable in humans. [18F]fleroxacin was synthesized and shown to be identical physically, chemically, and in its antimicrobial activity to the commercially produced product. Tracer amounts of [18F]fleroxacin were coinjected with a pharmacologic dose of unlabeled drug (10 mg/kg) into normal mice, rats with focal thigh infection due to Escherichia coli, and normal and infected rabbits. The rats and mice were killed at fixed time intervals after injection, and the concentration of drug was determined by radioactive counting in a well-type counter; the rabbits were studied both by this method and by positron emission tomographic (PET) imaging. These studies validated the reliability of the new approach and suggested that it could be applied safely to humans. In all three animal species studied, delivery of [18F]fleroxacin to most tissues was rapid, with the notable exception of the brain. Accumulation of drug in infected thigh muscle was similar to that in normal muscle. The concentrations of drug reached in various tissues suggest that fleroxacin will be particularly useful in the treatment of gastrointestinal, urinary tract, hepatobiliary, and skeletal infections and that it shows promise for the treatment of lung and soft tissue infection. The minimal concentrations of drug delivered to the brain should decrease the occurrence of central nervous system toxicity with this particular fluoroquinolone.