家兔经口染毒溴敌隆的代谢动力学研究  

Study on the pharmacokinetics of bromadiolone in oral poisoning rabbits

作　　者：蒋绍锋[1] 张驭涛 孙健[1] 张晶[2] 张宏顺[1] Jiang Shaofeng;Zhang Yutao;Sun Jian;Zhang Jing;Zhang Hongshun(National Institute of Occupational Health and Poison Control,China CDC,Beijing 100050,China;Beijing Center for Diseases Prevention and Control,Beijing 100013,China)

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [2]北京市疾病预防控制中心,100013

出　　处：《中华劳动卫生职业病杂志》2020年第6期444-446,共3页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的探讨溴敌隆经口灌胃染毒后,家兔体内溴敌隆血药浓度变化及代谢特点,以期为溴敌隆体内代谢研究提供参考。方法将普通级雄性日本大耳兔随机分为试剂对照组(无水乙醇1 g/kg)、高剂量组(溴敌隆0.3 mg/kg)和低剂量组(溴敌隆0.05 mg/kg),每组6只。分别于经口灌胃染毒后1、2、4、8、12、16、24、36、48、72、168、336、504 h从家兔耳中央动脉采血,样品1 h内离心,测定凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及血浆中溴敌隆浓度,借助DAS 3.0.2软件对染毒时间、血药浓度等代谢动力学数据进行分析。结果各组家兔染毒前后体重变化差异无统计学意义(P>0.05)。高、低剂量组家兔PT、APTT均出现明显异常,但PT出现异常早于APTT。高、低剂量组家兔均在染毒后12 h血浆中溴敌隆浓度达峰值,高剂量组溴敌隆半吸收期(t1/2ka)为4.34 h,清除半衰期(t1/2)为81.52 h;低剂量组t1/2Ka为6.90 h,t1/2为56.38 h。家兔经口染毒溴敌隆房室模型呈三室模型分布。结论溴敌隆口服吸收迅速,但代谢缓慢,溴敌隆经口染毒在体内变化符合三室模型。Objective To investigate the variations of bromadiolone concentration in blood and its metabolism in rabbits after oral administration of bromadiolone,and to provide reference for the study of bromadiolone metabolism.Methods Designed absolute alcohol(1 g/kg)reagent control group,high dose(0.3 mg/kg)and low dose group(0.05 mg/kg),there were 6 rabbits in each group.Blood samples were collected from the rabbit central auricular artery at regular intervals as 1 h,2 h,4 h,8 h,12 h,16 h,24 h,36 h,48 h,72 h,168 h,336 h,504 h after oral administration.The samples were centrifuged within 1 h.Prothrombin time(PT),activated partial thromboplastin time(APTT)and concentrations of bromadiolone in plasma were tested.Metabolic kinetics data was analyzed by DAS 3.0.2 software.Results Bromadiolone had no significant effect on the body weight of the experimental rabbits during the experimental period(P>0.05).PT and APTT were significantly abnormal in different dose groups,but for occurrence of exception,PT was earlier than APTT.The concentration of bromadiolone in plasma reached the peak value 12 h after gavage in both high-dose and low-dose groups.The absorption time of t1/2Ka in high-dose group was 4.34 h,the clearance time of t1/2 was 81.52 h,the absorption time of t1/2Ka in low-dose group was 6.90 h,and the elimination time of t1/2 was 56.38 h.The atrioventricular model of bromadidone was three compartment model in rabbits.Conclusion Bromadiolone can be absorbed rapidly by oral administration,but its metabolism is slow.The change of bromadiolone in vivo accords with the three compartment model.

关 键 词：中毒 溴敌隆 兔 药代动力学 药动学 

分 类 号：R99[医药卫生—毒理学]