Evaluation of toxicokinetic variables and arthropathic changes in juvenilerabbits after oral administration of an investigational fluoroquinolone, PD 117596
Rj. Johnson et al., Evaluation of toxicokinetic variables and arthropathic changes in juvenilerabbits after oral administration of an investigational fluoroquinolone, PD 117596, AM J VET RE, 61(11), 2000, pp. 1396-1402
Objective-To compare toxicokinetic variables and associated tissue drug con
centrations 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-b
earing joints, and tissue specimens were collected (60 minutes after drug a
dministration). Serum and tissue drug concentrations were determined by mic
robiologic plate assay.
Results-Macroscopically, treatment rabbits had a high prevalence of arthrop
athy 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 i
dentified in the midzone or close to the zone of calcified cartilage of tre
atment rabbits. Chondrocyte cellularity was reduced in affected areas, and
perivesicular regions had reduced staining with Safranin O. Correlation ana
lysis 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.