PHARMACOKINETIC DISPOSITION AND ARTHROPATHIC POTENTIAL OF ORAL OFLOXACIN IN DOGS

We examined the relation between the pharmacokinetic disposition and a rthropathic potential of ofloxacin, a new quinolone antibacterial agen t, using both male immature (3-month-old) and mature (18-month-old) be agles. Ofloxacin was orally administered to these dogs at 20 mg/kg onc e daily for 8 consecutive days, and the animals were killed 2 h after the last treatment. Serum ofloxacin concentrations were repeatedly mea sured on days 1 and 7 by use of high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated. In addition, on day 8, the drug concentrations in the joint synovial fluid and hume ral and femoral condyles were measured, Clinico-pathological tests of blood and serum or histopathological examination of bone specimens wer e also performed. Arthropathy was macroscopically observed in the cart ilage surface of all immature dogs, but: not in mature dogs. There wer e, however, no noticeable differences in pharmacokinetic parameters be tween the two age groups of dogs or between single and 7-day treatment s. In contrast to the occurrence of arthropathic lesions, the synovial fluid and condylar drug concentrations in immature dogs was equal to or lower than those in mature dogs, suggesting that the pharmacokineti c disposition of ofloxacin may not be essential for cartilage lesions.