Rausch-Derra Lesley C, Huebner Margie, Rhodes Linda
Am J Vet Res. 2015 Oct;76(10):853-9. doi: 10.2460/ajvr.76.10.853.
To investigate the safety of daily oral administration of grapiprant to dogs.
Thirty-six 9-month-old Beagles of both sexes.
Dogs were randomly assigned to groups that received grapiprant via oral gavage at 0, 1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group, which included 4 additional dogs that were monitored for an additional 30 days after treatment concluded (recovery period). All dogs received ophthalmologic, ECG, and laboratory evaluations before treatment began (baseline) and periodically afterward. All dogs were observed daily. Dogs were euthanized at the end of the study for necropsy and histologic evaluation.
All dogs remained clinically normal during treatment, with no apparent changes in appetite or demeanor. Emesis and soft or mucoid feces that occasionally contained blood were observed in all groups, although these findings were more common in dogs that received grapiprant. In general, clinicopathologic findings remained within baseline ranges. Drug-related changes in serum total protein and albumin concentrations were detected, but differences were small and resolved during recovery. No drug-related gross or microscopic pathological changes were detected in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the 50 mg/kg group.
Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.
研究犬每日口服格拉匹普兰的安全性。
36只9月龄的比格犬，雌雄均有。
将犬随机分为几组，分别通过口服灌胃给予0、1、6或50mg/kg的格拉匹普兰（总体积为5mL/kg），每24小时给药1次，持续9个月。每组包含每种性别的4只犬（即每组8只犬），50mg/kg组除外，该组在治疗结束后（恢复期）还额外包括4只犬，并对其进行了30天的监测。所有犬在治疗开始前（基线）及之后定期接受眼科、心电图和实验室评估。每天对所有犬进行观察。在研究结束时对犬实施安乐死以进行尸检和组织学评估。
所有犬在治疗期间临床状态均保持正常，食欲和行为举止无明显变化。所有组均观察到呕吐以及偶尔含有血液的软便或黏液便，不过这些发现更多见于接受格拉匹普兰的犬。总体而言，临床病理检查结果仍在基线范围内。检测到血清总蛋白和白蛋白浓度与药物相关的变化，但差异较小且在恢复期得到缓解。除50mg/kg组1只犬的回肠出现轻度黏膜再生外，在组织样本中未检测到与药物相关的大体或微观病理变化。
结果表明犬长期口服格拉匹普兰具有安全性。格拉匹普兰治疗犬骨关节炎的疗效需要在其他研究中进行评估。
