PD-117596

A series of 48 quinolone derivatives and their analogs were studied to examine the quant. relationship between the structure and antibacterial activity (ABA) using a new method called BiS, which includes a model of the receptor.BiS method allows the quant. evaluation of the structure-ABA relationship.It was demonstrated that the characteristics of the interaction between the model receptor and quinolone mols. are correlated with the given biol. activity.The results are consistent with the well-known mechanism of the antibacterial action of quinolone derivativesThe obtained math. model can be used for predicting the antibacterial activity of new compounds

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 or erosions. Histologically, vesicles were identified in the midzone or close to the zone of calcified cartilage of treatment rabbits. Chondrocyte cellularity was reduced in affected areas, and perivesicular regions had reduced staining with Safranin O. Correlation analysis of area under the curve values with total scores for lesion severity had a significant positive relationship.Conclusions—Our findings support the use of juvenile rabbits as a model for arthropathic changes induced by fluoroquinolone administration. (Am J Vet Res 2000;61:1396–1402)