盐酸丁卡因胃/肠镜润滑剂在比格犬体内的药动学和毒性研究

Pharmacokinetics and Toxicity Study of Tetracaine Hydrochloride Gastric/Enteroscopy Lubricant in Beagle Dogs

通过对比格犬单次灌胃或直肠给予盐酸丁卡因胃/肠镜润滑剂,观察动物的临床反应,测定盐酸丁卡因在体内的浓度,对主要的组织脏器进行大体剖检,并测量脏器重量及系数,以了解其在动物体内的药动学和毒性反应.将8只普通级比格犬,随机分为灌胃组和直肠组,每只犬分别单次灌胃或直肠给予10 mL盐酸丁卡因胃/肠镜润滑剂(含盐酸丁卡因80 mg).结果显示,各动物的外观体征、行为活动、呼吸和粪便等均未见明显异常,摄食正常,体重正常增长;与给药前相比,各动物在给药后4 h体温下降、心率减慢、Q-T间期和T波时间延长,为盐酸丁卡因的麻醉药效作用所致;各动物的血液学、血液生化学、主要脏器重量和系数及大体剖检均未见明显异常;单次灌胃或直肠给予后的平均达峰时间分别为0.63和0.44 h,平均消除半衰期分别为1.20和3.36 h,平均药时曲线下面积分别为60.44和60.19μg/L*h,提示吸收进入血液的药量较少,大部分留在局部发挥润滑和麻醉作用.

By administering tetracaine hydrochloride gastric/enteroscopy lubricant with single gavage or rectum,observing the clinical response of the animals,and measuring the concentration of tetracaine hydrochloride in the body,gross necropsy of the main tissue organs was performed,and the weight and coefficient of the organs were measured in order to understand the pharmacokinetics and toxicity in the animals.8 Beagle dogs were randomly divided into gavage group and rectal group.10 mL tetracaine hydrochloride gastric/enteroscopy lubricant(tetracaine hydrochloride 80 mg)was administered in gavage or rectum separately.The results show that there are unobvious abnormality,such as signs,behavioral activities,breathing,feces,the feeding and wight grouth of the dogs were pretty normal.Compared with pre-drug administration,each dog had significantly decreasing body temperature,slowing of heart rate,and prolonged Q-T interval and T wave time at 4 h after drug administration,it was caused by the anesthetic efficacy effect of tetracaine hydrochloride.Hematology,blood biochemistry,main organ weight and coefficient and gross dissection of each animal showed no obvious abnormalities;after a single gavage or rectal administration,the mean T max was 0.63 and 0.44 h,the mean t 1/2βwas 1.20 and 3.36 h;the mean AUC was 60.44 and 60.19μg/L*h,respectively.This suggested that less amount of drug was absorbed into the blood,and most of the drug remained for local lubrication and anesthesia.