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

Abstract

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.

ANIMAL:

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.

• Authors: R J Johnson, W D Black, R E Sigler, V M Baragi, A W Gough
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 61 Issue 11 Pg. 1396-402 (Nov 2000) ISSN: 0002-9645 [Print] United States
• PMID: 11108186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Drugs, Investigational
• Fluoroquinolones
• Quinolones
• PD-117596

Topics

• Administration, Oral
• Animals
• Anti-Infective Agents (administration & dosage, pharmacokinetics, toxicity)
• Cartilage, Articular (drug effects, metabolism)
• Chondrocytes (drug effects)
• Drug Evaluation (veterinary)
• Drugs, Investigational (administration & dosage, pharmacokinetics, toxicity)
• Fluoroquinolones
• Joints (drug effects, metabolism)
• Kidney (metabolism)
• Male
• Quinolones (administration & dosage, pharmacokinetics, toxicity)
• Rabbits (metabolism)
• Weight-Bearing