巴氯芬注射液Beagle犬腰椎穿刺置管多次鞘内注射局部刺激性研究

目的模拟临床给药途径,Beagle犬腰椎穿刺置管多次鞘内注射巴氯芬注射液,观察其局部刺激性,同时进行犬行为学观察,为巴氯芬注射液安全性评价提供依据。方法12只Beagle犬分为假手术组,生理盐水对照组,巴氯芬给药组。行腰椎穿刺置管,使用单通道微量注射泵泵入给药,给药剂量为1000μg/d,生理盐水对照组给予生理盐水0.5mL,连续给药7d,恢复期7d。每日进行行为学观察,给药结束及恢复期结束时每组麻醉2只动物,取给药部位脊髓进行组织病理学检查。结果给药及恢复期期间动物行为未见异常,给药结束时各组均有部分动物观察到置管处表皮感染现象,进行局部消毒处理后在恢复期第3天恢复正常。组织病理学检查发现给药及恢复期结束时各组动物脊髓均可见血管周围炎细胞浸润或脊髓内钙盐沉积,各组无差别。给药结束时巴氯芬组1例动物脊膜处有肉芽组织形成,判定与置管操作有关。结论巴氯芬注射液Beagle犬腰椎穿刺置管连续7d鞘内注射,给药剂量为1000μg/d对脊髓无局部刺激性作用,动物行为也未见异常。

Local Irritation Test of Baclofen Solution Repeated Lumbar Intrathecal Injection Administration in Beagle Dogs

Objective To determine the local irritation of baclofen solution repeated lumbar intrathecal injection in beagle dogs, together with behaviour observation, which provide information for Baclofen＇ s safety evaluation. Methods 12 beagle dogs were assigned into three groups： sham operated group, normal saline control group and baclofen group. Dogs with lumbar intrathecal catheters received baclofen solution at 1000 μg （baclnfen group） or normal saline 0.5 mL （normal saline control group） intrathecally by a single-channel infusion microinjection pump once a day for 7 days, with 7 days recovery period. We evaluated the behavioral side effects every day. On the 7th day and end of recovery period, the lumbar spinal cord was removed from 2 randomly selected dogs in each group for histological examination. Results No dogs showed any behavioral side effects associated with baclofen. At the end of dosing, slightly epidermal infection around catheters site were observed of each group and recovered nearly 3 days later after local disinfection treatment. Histologically, slight inflammatory cell infiltration and calcium mineralization occurred, similarly in both groups. On 7th day, one case of formation of granulation tissue in spinal meninges was abserved in baclofen group, which may be associated with the catheter placing. Conclusion Administration of Baclofen solution 1000μg once a day for 7 days did not induce irritation effect in the spinal cord and caused no behavioral side effects.