灌胃吡喹酮在中华草龟体内的代谢动力学研究  

Pharmacokinetics of praziquantel in turtle Chinemys reevesiis by intragastric administration

作　　者：张晓雨 庞溦 潘连德[1,2,3] 鲍晓颖 ZHANG Xiaoyu;PANG Wei;PAN Liande;BAO Xiaoying(Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources,Ministry of Education,Shanghai Ocean University,Shanghai 201306,China;National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University,Shanghai 201306,China;National Pathogen Collection Center for Aquatic Animals,Shanghai Ocean University,Shanghai 201306,China)

机构地区：[1]上海海洋大学省部共建水产种质资源发掘与利用教育部重点实验室,上海201306 [2]上海海洋大学水产科学国家级实验教学示范中心,上海201306 [3]上海海洋大学国家水生动物病原库,上海201306

出　　处：《大连海洋大学学报》2020年第1期89-95,共7页Journal of Dalian Ocean University

基　　金：国家自然科学基金资助项目(39970582);水产动物遗传育种上海市协同创新中心(ZF1206)

摘　　要：为探索吡喹酮(Praziquantel)对龟鳖临床驱虫的安全及有效使用,试验设4组,采用胃插管方式给中华草龟Chinemys reevesiis(雌、雄龟体质量平均为0.745、0.361 kg)灌胃吡喹酮驱虫药,在给药前后设定10个采血时间点(0~96 h),于背颈静脉窦连续采血,采用液相色谱-质谱联用法(LC-MS)测定中华草龟血浆内的吡喹酮药物浓度,用Kinetic 4.4药代分析软件进行模型分析和参数计算,比较不同性别、不同剂量、不同给药次数对吡喹酮在中华草龟体内的药物代谢动力学特征与不良反应的影响。结果表明:灌胃吡喹酮在中华草龟体内的药时数据符合一室开放模型,并出现了双峰效应,首峰位于0.5 h(试验Ⅰ、Ⅱ、Ⅳ组)或3 h(试验Ⅲ组),第二峰位于12 h(试验Ⅰ组和Ⅳ组)和72 h(试验Ⅱ组和Ⅲ组);获得4个试验组的主要药动学参数,试验Ⅰ组[剂量30 mg/kg(体质量),单次,雌性]的T max=15.949 h、C max=0.615μg/mL、AUC=26.664μg/(mL·h),试验Ⅱ组(剂量30 mg/kg,单次,雄性)的T max=74.857 h、C max=0.592μg/mL、AUC=123.427μg/(mL·h),试验Ⅲ组(剂量15 mg/kg,单次,雄性)的T max=75.523 h、C max=0.234μg/mL、AUC=48.760μg/(mL·h),试验Ⅳ组(剂量10 mg/kg,3次,雌性)的T max=14.161 h、C max=0.303μg/mL、AUC=15.726μg/(mL·h);经灌胃给药,中华草龟对吡喹酮的吸收慢且少,但分布相对较广,雄性中华草龟的吸收速率、消除速率均小于雌性,雌、雄龟的吸收代谢水平存在显著性差异(P<0.05);单次给药组(剂量15、30 mg/kg)的试验龟均出现了强烈的不良反应,剖检发现,肝脏、肾脏、肌肉等组织器官均出现不同程度的病变或坏死;多次给药组(剂量10 mg/kg,3次)仅有一只(A4,192 h)出现轻度不良反应。研究表明,龟鳖临床上使用吡喹酮驱虫,推荐单次灌胃剂量为10 mg/kg(体质量)以下,如需要提高剂量可多次给药,给药次数控制在3次以内,给药间隔时间为3 h以上。Turtle Chinemys reevesiis with body weight(BW)of 0.745 kg(♀)and 0.361 kg(♂)were forced to take praziquantel by intragastric perfusion at a dose of 30 mg/kg BW(group Ⅰ and group Ⅱ),respectively,the male turtle was administrated by intragastric perfusion at a dose 15 mg/kg(group Ⅲ)and the female turtle was administrated three times,0.05,3.05,and 6.05 h after blood sampling,by intragastric perfusion at a dose of 10 mg/kg(group Ⅳ,a total of 30 mg/kg)to provide scientific guidance for the safe and effective use of praziquantel in the clinical deworming of turtles.The blood was sampled from the dorsal jugular sinus in the turtle in the groups Ⅰ,Ⅱ,Ⅲ and Ⅳ 0,0.5,1,3,6,12,24,48,72,and 96 h after administration,and then the concentration of praziquantel in the plasma of the turtle was determined by liquid chromatography-mass spectrometry(LC-MS)to investigate the pharmacokinetics of praziquantel in different gender turtles by various doses and times of intragastric administration by Kinetic 4.4 software.The results showed that the drug-time data of praziquantel in the turtle conformed to the one-compartment open model,with bimodal effect:the first peak at 0.5 h in groups Ⅰ,Ⅱ,and Ⅳ or 3 h in group Ⅲ;the second peak at 12 h in groups Ⅰ and Ⅳ and 72 h in groups Ⅱ and Ⅲ.The main pharmacokinetic parameters in the four groups were described as follows:Tmax=15.949h,Cmax=0.615μg/mL,AUC=26.664μg/(mL)in group Ⅰ(dose 30 mg/kg,single,female);T max=74.857 h,C max=0.592μg/mL,AUC=123.427μg/(mL·h)in group Ⅱ(dose 30 mg/kg,single,male);T max=75.523 h,C max=0.234μg/mL,AUC=48.760μg/(mL·h)in group Ⅲ(dose 15 mg/kg,single,male);and T max=14.161 h,C max=0.303μg/mL,AUC=15.726μg/(mL·h)in group Ⅳ(dose 10 mg/kg,3 times,female).Intragastric administration revealed that the turtle had slower and less absorption of praziquantel,with relatively wide distribution.There were less absorption rate and elimination rate in the male than those in the females,with significantly different absorption and metabo

关 键 词：中华草龟 吡喹酮 驱虫药 药物代谢动力学 不良反应 双峰效应 

分 类 号：S948[农业科学—水产养殖]