title: Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596.
abstract: To study the potential of the fluorquinolone, PD 117596 to cause arthropathy in experimental animals, immature rabbits were orally administered the drug for five days at 0, 100, 350, 500 and 750 mg/kg. Characterization of changes induced in major synovial joints was based on: macroscopic and histopathologic observations, transmission electron microscopic examinations and magnetic resonance imaging. Preferentially targeting 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. Ultrastructurally, hypertrophic chondrocytes were the consequence of karyomegaly and RER proliferation. Matrix density was reduced due to collagen and proteoglycan loss. Joint structures were readily visualized by magnetic resonance imaging which identified thickened articular cartilage, surface irregularities consistent with ruptured vesicles and separation of opposing articular surfaces secondary to synovival effusions. The immature rabbit, although less sensitive than the juvenile dog to the arthropathic effects of quinolones, was nonetheless a good model to study this experimental osteoarticular disease.
authors.affiliation: Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Ann Arbor, MI 48105, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gough
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.forename: E
authors.initials: E
authors.lastname: Campbell
authors.forename: L
authors.initials: L
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Tylor
authors.forename: A
authors.initials: A
authors.lastname: Carpenter
authors.forename: W
authors.initials: W
authors.lastname: Black
authors.forename: P K
authors.initials: PK
authors.lastname: Basrur
authors.forename: V M
authors.initials: VM
authors.lastname: Baragi
authors.forename: R
authors.initials: R
authors.lastname: Sigler
authors.forename: A
authors.initials: A
authors.lastname: Metz
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001168:Arthritis / Q000139:chemically induced* / Q000473:pathology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D024841:Fluoroquinolones; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D015363:Quinolones / Q000009:adverse effects*; D011817:Rabbits
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C057711:PD-117596