摘要
目的研究醒脑静注射液对Beagle犬心血管和呼吸系统的影响。方法已成功埋入植入子的Beagle犬6只,拉丁方设计给药,设溶媒对照组,辅料对照组,醒脑静注射液1(XNJI1,含人工麝香)高、中、低剂量(1.41、0.71、0.35 mg/kg)组和醒脑静注射液2(XNJI2,含天然麝香)高、中、低剂量(1.46、0.73、0.36 mg/kg)组,XNJI1高、中、低剂量均约为人临床等效剂量的5.2、2.6、1.3倍;XNJI2高、中、低剂量均约为人临床等效剂量的5.1、2.6、1.3倍。辅料对照组给予等体积的0.5%聚山梨酯80溶液;溶媒对照组给予等体积氯化钠注射液。前肢iv给药,每2个给药组设1 d洗脱期。利用DSI遥测系统连续测量给药前1 h至给药后4 h的心电、血压、呼吸等指标。结果各给药组及辅料对照组部分Beagle犬出现明显过敏症状,在给药后均出现持续10~45 min的口鼻部发红肿胀、瘙痒,部分表现烦躁不安,辅料对照组最为明显。与溶媒对照组比较,XNJI1高剂量组及辅料对照组心率显著升高(P<0.05、0.01),分别于给药后30 min、1 h恢复至给药前水平;辅料对照组给药后5、10、30 min QTc间期显著延长(P<0.01);XNJI1高剂量组给药后10 min、0.5 h呼吸频率(BPM)显著升高,XNJI2高剂量组给药后5 min BPM显著升高(P<0.05、0.01),辅料对照组给药后BPM明显升高但无显著差异。XNJI1比XNJI2在心率、QTc间期、BPM等方面波动较大,但二者无显著差异。结论给予大剂量醒脑静注射液,Beagle犬出现不同程度类过敏反应症状及心电呼吸影响可能与辅料聚山梨酯80有关,临床使用应密切监测相关指标以确保用药安全。
Objectlve To investigate the effect of Xingnaojing Injection(XNJI)on cardiovascularand respiratory function in Beagle dogs.Methods Six Beagles implanted with implants were setted as vehicle group(normal salin),excipient group(0.5%polysorbate80)and low(0.35,0.36 mg/kg),middle(0.71,0.73 mg/kg),high(1.41,1.46 mg/kg)dose test groups of sample 1,2 by Latin square.the dogs were administered intravenously with one day washout period for each two groups.The DSI physiological signal telemetrySystem was used to continuously measure the ECG,blood pressure,and respiration from 1 h before administration to 4 h after administration.Results Some Beagle dogs in each administration group and excipient control group had obvious allergic symptoms,and the mouth and nose redness,swelling and pruritus lasted for 10-45 minutes after administration,and some of them showed irritability and restlessness,especially in the adjuvant control group.Compared with the vehicle control group,the heart rate of XNJI1 high-dose group and excipient control group was significantly increased(P<0.05,0.01),and returned to the level before administration at 30 min and 1 h after administration;QTc interval at 5,10 and 30 min in excipient control group was significantly prolonged(P<0.01);respiratory rate(BPM)at 10 min and 0.5 h after administration in XNJI1 high-dose group was significantly increased,and 5 min after administration in XNJI2 high-dose group BPM increased significantly(P<0.05,0.01),The BPM in the adjuvant control group increased significantly after administration,but there was no significant difference.Compared with XNJI2,XNJI1 fluctuated more in heart rate,QTc interval and BPM,but there was no significant difference between them.Conclusion The anaphyl-actoid symptoms and ECG respiratory effect of XNJI on Beagle dogs were related to polysorbate 80,and the relevant indexes should be monitored closely to ensure the safety ofclinical medication.
作者
李莎莎
王虎斌
丁亚军
刘晶
樊昌艳
LI Shasha;WANG Hubin;DING Yajun;LIU Jing;FAN Changyan(China Pharmaceutical University,Nanjing 211198,China;Jiangsu Pharmaceutical Research Institute Co.Ltd,Nanjing 210009,China)
出处
《药物评价研究》
CAS
2020年第12期2422-2428,共7页
Drug Evaluation Research
基金
江苏省政策引导类计划项目[产学研合作——前瞻性联合研究项目(BY2016017-01)]。
