唑拉西泮和替来他明对中华草龟的麻醉效果及其药物代谢动力学
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摘要
为了解龟类临床兽医学的麻醉术问题,根据预实验结果选择动物医学推荐的临床麻醉药物舒泰(唑拉西泮:替来他明=1∶1)对中华草龟进行麻醉实验,比较不同注射剂量的舒泰对中华草龟的麻醉效果,并使用高效液相色谱法(HPLC)测定舒泰中唑拉西泮和替来他明在中华草龟血浆中的浓度,用药物代谢动力学软件PKsolver 2.0来分析其药物代谢动力学特征。结果发现,肌肉注射舒泰剂量为25 mg/kg时,对中华草龟麻醉的诱导期、麻醉期和苏醒期的时长分别为0.42、4.33和4.14 h,舒泰对中华草龟的麻醉效果较好,符合临床手术的要求。唑拉西泮和替来他明在中华草龟体内的药时曲线均符合一次式二室开放模型,唑拉西泮的药物代谢动力学方程为C=13.462e~(–0.223t)+2.127e~(–0.055t),主要药物代谢动力学参数为达峰浓度C_(max)=11.695μg/mL、达峰时间T_(max)=1.060 h和药时曲线下面积AUC=92.470μg/(mL·h);替来他明的药物代谢动力学方程为C=10.619e–0.203t+0.279e–0.047t,主要药物代谢动力学参数为达峰浓度Cmax=9.654μg/mL、达峰时间Tmax=0.482 h和药时曲线下面积AUC=56.348μg/(mL·h)。结合麻醉效果分析,唑拉西泮和替来他明血药浓度分别达到8.12和8.96μg/mL时,可以使健康的中华草龟进入麻醉期,为维持麻醉状态,唑拉西泮和替来他明的血药浓度应不低于7.18和4.73μg/mL。
The current study aimed to solve the problems of anaesthesia in clinical veterinary medicine of turtles.According to the results of pre-experiment, we selected the animal medicine recommended clinical anaesthetic drugs Telazol(tiletamine:zolazepam=1:1). We compared the anaesthetic effects of different dosages of Zoletil on Chinemys reevesiis, and the concentrations of zolazepam and tiletamine in plasma were detected by High Performance Liquid Chromatogram(HPLC), and analyzed with software PKsolver 2.0 to research the features of pharmacokinetics. Zoletil at a rate of 25 mg/kg was administered intramuscularly to C. reevesiis.The induction time, anaesthesia time and recovery time were 0.42, 4.33 and 4.14 h respectively. Zoletil on C. reevesiis anaesthesia was better, in line with the requirements of clinical surgery. The concentration-time curves of zolazepam and tiletamine in plasma all were conformed to a two-compartment open model. And the concentrationtime equations of zolazepam and tiletamine were C=13.462 e~(–0.223) t+2.127 e~(–0.055) t, C=10.619 e~(–0.203) t+0.279 e~(–0.047) t,respectively. The major pharmacokinetic parameters were as follows: Cmax=11.695 μg/mL, Tmax=1.060 h and AUC=92.470 μg/(mL·h) in zolazepam; C_(max)=9.654 μg/mL, T_(max)=0.482 h and AUC=56.348 μg/(mL·h) in tiletamine. It suggested that blood concentration of zolazepam and tiletamine all reached 8.12 μg/mL and 8.96 μg/mL, respectively, which could cause healthy C. reevesiis into anaesthesia. To maintain anaesthesia, the blood concentrations of zolazepam and tiletamine should not be less than 7.18 μg/mL and 4.73 μg/mL.
The current study aimed to solve the problems of anaesthesia in clinical veterinary medicine of turtles.According to the results of pre-experiment, we selected the animal medicine recommended clinical anaesthetic drugs Telazol(tiletamine:zolazepam=1:1). We compared the anaesthetic effects of different dosages of Zoletil on Chinemys reevesiis, and the concentrations of zolazepam and tiletamine in plasma were detected by High Performance Liquid Chromatogram(HPLC), and analyzed with software PKsolver 2.0 to research the features of pharmacokinetics. Zoletil at a rate of 25 mg/kg was administered intramuscularly to C. reevesiis.The induction time, anaesthesia time and recovery time were 0.42, 4.33 and 4.14 h respectively. Zoletil on C. reevesiis anaesthesia was better, in line with the requirements of clinical surgery. The concentration-time curves of zolazepam and tiletamine in plasma all were conformed to a two-compartment open model. And the concentrationtime equations of zolazepam and tiletamine were C=13.462 e~(–0.223) t+2.127 e~(–0.055) t, C=10.619 e~(–0.203) t+0.279 e~(–0.047) t,respectively. The major pharmacokinetic parameters were as follows: Cmax=11.695 μg/mL, Tmax=1.060 h and AUC=92.470 μg/(mL·h) in zolazepam; C_(max)=9.654 μg/mL, T_(max)=0.482 h and AUC=56.348 μg/(mL·h) in tiletamine. It suggested that blood concentration of zolazepam and tiletamine all reached 8.12 μg/mL and 8.96 μg/mL, respectively, which could cause healthy C. reevesiis into anaesthesia. To maintain anaesthesia, the blood concentrations of zolazepam and tiletamine should not be less than 7.18 μg/mL and 4.73 μg/mL.
引文
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[8]徐培培,林启存,潘连德.中华鳖脾肾性水肿病病理学诊断[J].水产学报,2015,39(7):1054-1061.Xu P P, Lin Q C, Pan L D. Histopathological diagnosis on spleen-and-kidney-induced edema of Pelodiscus sinensis[J]. Journal of Fisheries of China, 2015, 39(7):1054-1061(in Chinese).
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[17]钟亚方,王洪斌,范宏刚,等.小型猪血浆中舒泰两种成分测定方法的建立[J].黑龙江畜牧兽医,2008(11):65-66.Zhong Y F, Wang H B, Fan H G, et al. A method established for determination of two kinds of components of Zoletil in miniature pig plasma[J]. Heilongjiang Animal Science and Veterinary Medicine,2008(11):65-66(in Chinese).
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[20]周赞,蔡梦思,刘虞,等.红耳滑龟和中华草龟幼体体温与运动的热依赖性、补偿生长及免疫力[J].生态学报,2016, 36(21):7014-7022.Zhou Z, Cai M S, Liu Y, et al. Body temperature, thermal dependence of locomotor performance, compensatory growth, and the immunity of hatchling red-eared turtles and Chinese pond turtles[J]. Acta Ecologica Sinica, 2016, 36(21):7014-7022(in Chinese).
[21]贺刚,何力,方春林,等.中华草龟(♀)与中华花龟(♂)及其杂种F1代染色体及同工酶比较[J].淡水渔业,2012,42(2):3-9.He G, He L, Fang C L, et al. The karyotype and Isozymes of hybrid turtle(Chinemys reevesii♀×Ocadia sinensis♂)and comparison with their parents[J]. Freshwater Fisheries, 2012, 42(2):3-9(in Chinese).
[22]黄春红,罗玉双,韩庆,等.人工养殖中华草龟的营养成分与食用价值[J].江苏农业科学,2017, 45(6):157-161.Huang C H, Luo Y S, Han Q, et al. Nutritional ingredients and edible value of artificial cultured Chinese turtle[J]. Jiangsu Agricultural Sciences,2017, 45(6):157-161(in Chinese).
[23]张博.氯胺酮复合麻醉剂对小型猪麻醉效果及氯胺酮药代动力学的研究[D].哈尔滨:东北农业大学,2011.Zhang B. Anaesthetic effects of ketamine combined anesthetic and the pharmacokinetics study in miniature pigs[D]. Harbin:Northeast Agricultural University,2011(in Chinese).
[24]徐春忠,吴锋,文德亮,等.舒泰与氯胺酮对猎豹麻醉效果的比较[J].畜牧与兽医,2010, 42(5):88-91.Xu C Z, Wu F, Wen D L, et al. Comparison of anesthetic effects of Zoletil and ketamine on Acinonyx jubatus[J].Animal Husbandry&Veterinary Medicine, 2010, 42(5):88-91(in Chinese).
[25]覃筱燕,杨林,张淑萍,等.常用麻醉药物麻醉效果的比较[J].中央民族大学学报(自然科学版),2005, 14(3):264-268.Qin X Y, Yang L, Zhang S P, et al. Comparison between the effects of different anaesthetic in common use[J].Journal of the Central University For Nationalities(Natural Sciences Edition), 2005, 14(3):264-268(in Chinese).
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[2]陈晨,潘连德.宠物龟眼炎的病原鉴定及临床药物治疗的研究[J].上海海洋大学学报,2011,20(2):244-251.Chen C, Pan L D. Identification of pathogen from pet chelonian with ophthalmia and the clinic therapy[J].Journal of Shanghai Ocean University, 2011, 20(2):244-251(in Chinese).
[3]王伟喆,潘连德.东锦龟摩尔摩根氏菌的分离鉴定和药敏试验[J].江苏农业科学,2013,41(10):205-208.Wang W Z, Pan L D. Isolation, identification and drug sensitivity test of Morganella morganii of Chrysemys picta picta[J]. Jiangsu Agricultural Sciences, 2013,41(10):205-208(in Chinese).
[4]李玉平,赵凌恭,余春明,等.巴西龟肺炎、眼炎综合征的病理学观察[J].中国兽医杂志,2011,47(2):56-57.Li Y P, Zhao L G, Xu C M, et al. Pathological observation of red-eared pneumonia and ophthalmia syndrome[J]. Chinese Journal of Veterinary Medicine,2011,47(2):56-57(in Chinese).
[5]Moon P F, Stabenau E K. Anesthetic and postanesthetic management of sea turtles[J]. Journal of the American Veterinary Medical Association, 1996, 208(5):720-726.
[6]Norton T M. Chelonian emergency and critical care[J].Seminars in Avian and Exotic Pet Medicine,2005,14(2):106-130.
[7]陈彦伶,牟群,潘连德,等.中华鳖药源性肝病模型的构建及其病理学观察[J].大连海洋大学学报,2013,28(1):61-66.Chen Y L, Mou Q, Pan L D, et al. Establishment of drug-induced liver disease model and pathological observation in soft shell turtle Trionyx sinensis[J]. Journal of Dalian Ocean University, 2013, 28(1):61-66(inChinese).
[8]徐培培,林启存,潘连德.中华鳖脾肾性水肿病病理学诊断[J].水产学报,2015,39(7):1054-1061.Xu P P, Lin Q C, Pan L D. Histopathological diagnosis on spleen-and-kidney-induced edema of Pelodiscus sinensis[J]. Journal of Fisheries of China, 2015, 39(7):1054-1061(in Chinese).
[9]茅玲燕,潘连德.液相色谱串联质谱法研究恩诺沙星在中华草龟体内药物代谢动力学[J].水产学报,2019,43(4):1-8.Mao L Y, Pan L D. The pharmacokinetics of enrofloxacin in Chinemys reevesiis by HPLC-MS/MS[J]. Journal of Fisheries of China, 2019, 43(4):1-8(in Chinese).
[10]章宇思,潘连德,洪滨.连续肌注恩诺沙星对中华草龟的急性和慢性毒理研究[J].大连海洋大学学报,2017,32(6):643-650.Zhang Y S, Pan L D, Hong B. Acute and chronic toxicological effects of continuous intramuscular injection of enrofloxacin on Chinese pond turtle[J]. Journal of Dalian Ocean University, 2017, 32(6):643-650(in Chinese).
[11] Bennett R A, Schumacher J, Hedjazi-Haring K, et al.Cardiopulmonary and anesthetic effects of propofol administered intraosseously to green iguanas[J]. Journal of the American Veterinary Medical Association, 1998, 212(1):93-98.
[12] Sleeman J M,Gaynor J. Sedative and cardiopulmonary effects of medetomidine and reversal with atipamezole in desert tortoises(Gopherus agassizii)[J]. Journal of Zoo and Wildlife Medicine,2000, 31(1):28-35.
[13] Dennis P M, Heard D J. Cardiopulmonary effects of a medetomidine-ketamine combination administered intravenously in gopher tortoises[J]. Journal of the American Veterinary Medical Association, 2002, 220(10):1516-1519.
[14] Knotek Z. Alfaxalone as an induction agent for anaesthesia in terrapins and tortoises[J]. Veterinary Record,2014, 175(13):327.
[15]谢全森,李俊伟,杨振才.MS-222对中华鳖的麻醉效果研究[J].山西师范大学学报(自然科学版),2009, 23(1):78-81.Xie Q S, Li J W, Yang Z C. Anaesthetic effects of ms-222 on Chinese soft-shelled turtles[J]. Journal of Shanxi Normal University(Natural Science Edition), 2009,23(1):78-81(in Chinese).
[16] Semple H A, Gorecki D K, Farley S D, et al. Pharmacokinetics and tissue residues of Telazol in free-ranging polar bears[J]. Journal of Wildlife Diseases, 2000, 36(4):653-662.
[17]钟亚方,王洪斌,范宏刚,等.小型猪血浆中舒泰两种成分测定方法的建立[J].黑龙江畜牧兽医,2008(11):65-66.Zhong Y F, Wang H B, Fan H G, et al. A method established for determination of two kinds of components of Zoletil in miniature pig plasma[J]. Heilongjiang Animal Science and Veterinary Medicine,2008(11):65-66(in Chinese).
[18] Akkerdaas L C. Recent developments in domestic animal anesthesia[J]. Tijdschrift Voor Diergeneeskunde,2008, 133(24):1048-1054.
[19] Madbouly K, Alshahrani S, Al-Omair T, et al. Efficacy of local subcutaneous anesthesia versus intramuscular opioid sedation in extracorporeal shockwave lithotripsy:a randomized study[J]. Journal of Endourology, 2011,25(5):845-849.
[20]周赞,蔡梦思,刘虞,等.红耳滑龟和中华草龟幼体体温与运动的热依赖性、补偿生长及免疫力[J].生态学报,2016, 36(21):7014-7022.Zhou Z, Cai M S, Liu Y, et al. Body temperature, thermal dependence of locomotor performance, compensatory growth, and the immunity of hatchling red-eared turtles and Chinese pond turtles[J]. Acta Ecologica Sinica, 2016, 36(21):7014-7022(in Chinese).
[21]贺刚,何力,方春林,等.中华草龟(♀)与中华花龟(♂)及其杂种F1代染色体及同工酶比较[J].淡水渔业,2012,42(2):3-9.He G, He L, Fang C L, et al. The karyotype and Isozymes of hybrid turtle(Chinemys reevesii♀×Ocadia sinensis♂)and comparison with their parents[J]. Freshwater Fisheries, 2012, 42(2):3-9(in Chinese).
[22]黄春红,罗玉双,韩庆,等.人工养殖中华草龟的营养成分与食用价值[J].江苏农业科学,2017, 45(6):157-161.Huang C H, Luo Y S, Han Q, et al. Nutritional ingredients and edible value of artificial cultured Chinese turtle[J]. Jiangsu Agricultural Sciences,2017, 45(6):157-161(in Chinese).
[23]张博.氯胺酮复合麻醉剂对小型猪麻醉效果及氯胺酮药代动力学的研究[D].哈尔滨:东北农业大学,2011.Zhang B. Anaesthetic effects of ketamine combined anesthetic and the pharmacokinetics study in miniature pigs[D]. Harbin:Northeast Agricultural University,2011(in Chinese).
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