A Non-Arthropathic Dose and Its Disposition Following Repeated Oral Administration of Ofloxacin, a New Quinolone Antimicrobial Agent, to Juvenile Dogs

Journal of Veterinary Medical Science

Yoichi MURAKAMI¹  Kazuhisa FURUHAMA¹  Koichi YABE¹  Saori NISHIDA¹  Kosuke OKADA²  Masanobu GORYO²  Masayasu SEKIGUCHI¹ 

[1] Tokyo Research and Development Center, Daiichi Pharmaceutical Co., Ltd.;Department of Veterinary Pathology, Faculty of Agriculture, Iwate University

关键词: arthropathy;    juvenile dog;    non-arthropathic dose;    ofloxacin;    pharmacokinetics;   

DOI  :  10.1292/jvms.63.867

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(23)Cited-By(7)A non-arthropathic dose and disposition of ofloxacin, a potent new quinolone antimicrobial agent, were assessed in male juvenile (3-month-old) dogs, when administered orally at 5, 10 and 20 mg/kg/day once daily for 8 consecutive days. Ofloxacin concentrations in sera and articular cartilages were analyzed by high-performance liquid chromatography (HPLC). Macroscopically, arthropathy characterized by fluid-filled vesicles in articular surface of the humerus and femur was observed in animals receiving 10 and 20 mg/kg/day of ofloxacin, but not in those given 5 mg/kg/day. At 20 mg/kg/day, arthropathy of comparable severity also occurred on day 2. Microscopically, the cavity formation in the middle zone of the articular cartilage was first identified and then necrotic chondrocytes were found numerous around the cavity, followed by appearance of chondrocyte clusters. In pharmacokinetics, peak serum concentration (Cmax) and area under the concentrations (AUC0-24) were increased in a dose-dependent manner. However, no remarkable differences in these two parameters were noted between a single and repeated treatments, suggesting no accumulation of the drug. The articular ofloxacin concentration 2 hr after treatment was approximately 1.8 (day 2) to 2.0 times (day 8) higher than the serum concentration. Based on these results, a non-arthropathic dose of ofloxacin in male juvenile dogs following an 8-day treatment is considered to be 5 mg/kg/day, and its Cmax, AUC0-24 and articular cartilage concentrations 2 hr after treatment were 3.4 μg/ml, 35.1 μg·hr/m l and 7.0 μg/g, respectively, under these experimental conditions. Thus, arthropathy due to ofloxacin may be predicted by monitoring serum drug concentration.

【 授权许可】

Unknown