Effects of ciprofloxacin on joint cartilage in immature dogs immediately after dosing and after a 5-month treatment-free period.
A study in young beagle dogs was performed in which the animals were treated for 2 weeks with ciprofloxacin at oral doses of 0, 10, 30 or 90 mg/kg per day. Immediately after treatment half of the number of animals were killed and all weight-bearing joints were subject to a thorough gross and histopathological investigation, including special staining of the cartilage matrix, and immunohistochemistry as well as electron microscopy. The remaining animals were maintained for an additional 5-months treatment-free period before being killed. Again, all weight-bearing joints were subject to a thorough gross and histopathological investigation. After 14 days of treatment with ciprofloxacin, oral doses of 30 and 90 mg/kg induced the characteristic arthropathy (blisters, erosions) in juvenile beagle dogs. As expected the lesions persisted while the animals were growing. In contrast, and to our knowledge demonstrated for the first time, an oral dose of 10 mg/kg ciprofloxacin did not induce joint lesions after short-term treatment in juvenile beagle dogs and was also not associated with arthrotoxicity when the dogs became older.
von Keutz
Eckhard
E
PH-PDP Toxicology, Pharma Research Center, Bayer HealthCare AG, Aprather Weg, 42096, Wuppertal, Germany. eckhard.keutz@bayerhealthcare.com
Rühl-Fehlert
Christine
C
Drommer
Wolfgang
W
Rosenbruch
Martin
M
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005552:Forelimb; D006614:Hindlimb; D007592:Joint Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D013997:Time Factors
D000890:Anti-Infective Agents; D002939:Ciprofloxacin