Evaluation of toxicokinetic variables and arthropathic changes in juvenile rabbits after oral administration of an investigational fluoroquinolone, PD 117596.

Objective—To compare toxicokinetic variables and associated tissue drug concentrations with severity of articular lesions in weight-bearing joints of juvenile rabbits after oral administration of a fluoroquinolone. Animals—Ten 6- to 7-week-old, 800- to 1,200-g, New Zealand White rabbits. Procedures—Rabbits were gavaged daily with the fluoroquinolone PD 117596 at 500 mg/kg of body weight for 5 days. Blood samples were collected on day 4 at preestablished times, up to 24 hours after drug administration. On day 5 gross lesion severity and prevalence were evaluated in the major weight-bearing joints, and tissue specimens were collected (60 minutes after drug administration). Serum and tissue drug concentrations were determined by microbiologic plate assay. Results—Macroscopically, treatment rabbits had a high prevalence of arthropathy with the distal portion of the femur having the highest prevalence and severity of lesions. Grossly, alterations to articular cartilage included 1 to 4 mm in diameter vesicles o...