QUINOLONE ARTHROPATHY IN IMMATURE RABBITS TREATED WITH THE FLUOROQUINOLONE, PD-117596

To study the potential of the fluorquinolone, PD 117596 to cause arthr opathy in experimental animals, immature rabbits were orally administe red the drug for five days at 0, 100, 350, 500 and 750 mg/kg. Characte rization of changes induced in major synovial joints was based on: mac roscopic and histopathologic observations, transmission electron micro scopic examinations and magnetic resonance imaging. Preferentially tar geting the knee, PD 117596 produced vesicles and erosions in articular cartilage which resembled, morphologically, those described in other laboratory species. Lesion incidence was not clearly dose-related. In the perivesicular region, degenerate chondrocytes were intermixed with hypertrophic cartilage cells and chondrocyte clusters. Ultrastructura lly, hypertrophic chondrocytes were the consequence of karyomegaly and RER proliferation. Matrix density was reduced due to collagen and pro teoglycan loss. Joint structures were readily visualized by magnetic r esonance imaging which identified thickened articular cartilage, surfa ce irregularities consistent with ruptured vesicles and separation of opposing articular surfaces secondary to synovival effusions. The imma ture rabbit, although less sensitive than the juvenile dog to the arth ropathic effects of quinolones, was nonetheless a good model to study this experimental osteoarticular disease.