小型猪专用复合麻醉剂麻醉后阿替美唑的颉颃效果及其体内药代动力学

doi:10.11843/j.issn.0366-6964.2014.12.023

畜牧兽医学报 ›› 2014, Vol. 45 ›› Issue (12): 2074-2080.doi: 10.11843/j.issn.0366-6964.2014.12.023

小型猪专用复合麻醉剂麻醉后阿替美唑的颉颃效果及其体内药代动力学

姜胜，谭丽娟，李新，范宏刚，王洪斌^*

（东北农业大学动物医学学院，哈尔滨 150030）

收稿日期:2014-03-31 出版日期:2014-12-23 发布日期:2014-12-23
通讯作者: 王洪斌，教授，博士生导师，E-mail：hbwang1940@163.com
作者简介:姜胜（1986-），男，博士，主要从事动物麻醉与镇痛研究，E-mail：cjsheng@126.com
基金资助:
国家自然科学基金项目（31272617；31302150）

Antagonistic Effect of Atipamezole and Its Pharmacokinetics Following Anaesthesia with the Combined Anaesthetic for Miniature Pigs in Minipigs

JIANG Sheng，TAN Li-juan，LI Xin，FAN Hong-gang，WANG Hong-bin^*

(College of Veterinary Medicine，Northeast Agricultural University，Harbin 150030，China)

Received:2014-03-31 Online:2014-12-23 Published:2014-12-23

摘要/Abstract

摘要：

旨在观察阿替美唑颉颃小型猪专用复合麻醉剂（XFM）的效果，探讨阿替美唑在小型猪体内的药代动力学。14头小型猪，随机均分为阿替美唑组和对照组，小型猪耳根部肌肉注射阿托品后再肌注XFM对小型猪进行全身麻醉。麻醉30 min后阿替美唑组肌肉注射阿替美唑0.12 mg•kg^-1进行全麻催醒，对照组按同等剂量注射生理盐水。前腔静脉采集血样，并观察记录小型猪苏醒时间、心率和呼吸率变化，记录阿替美唑给药后小型猪镇痛、镇静、肌松、体位及听觉反射总得分，评价阿替美唑的催醒效果，同时用高效液相色谱法测定各采血时间点血浆药物浓度。结果表明，阿替美唑组小型猪苏醒时间显著短于对照组（P<0.05）；阿替美唑给药后5~60 min小型猪心率显著高于对照组（P<0.05）；呼吸频率在10~15 min显著高于对照组（P<0.05）；小型猪镇痛、镇静、肌松、体位及听觉反射总得分在阿替美唑给药后10~90 min显著低于对照组（P<0.05）；阿替美唑在血浆中吸收相半衰期（T_1/2α）为（11.056 9±3.093 4）min；消除相半衰期（T_1/2β）为（875.421 8±159.375 3）min；药时曲线下面积（AUC）为（797 958.836 0±96 783.124 1） pg•（min•mL）^－1；达峰时间（T_peak）为（9.544 0±0.484 4）min；达峰浓度（C_max）为（1 107.065 2 ± 121.620 1）pg•mL^－1。结果提示阿替美唑肌注小型猪后，其体内吸收迅速，分布广泛，在血浆中药物经时过程符合一级吸收二室开放模型，可迅速逆转XFM对小型猪的麻醉作用。

Abstract:

This study was conducted to investigate the antagonistic effect of atipamezole and following anaesthesia with the Combined Anaesthetic for Miniature Pigs (XFM) and its pharmacokinetics in minipigs.Fourteen pigs were randomly divided into control group and atipamezole group.All experiment pigs were anesthetised with XFM intramuscularly.Pigs in atipamezole group were administrated with atipamezole (0.12 mg•kg－1) intramuscularly and pigs in control group were administrated with saline.Baseline physiological parameters of respiration and heart rate were recorded and blood sample were collected from cranial vena cava and detected by using high performance liquid chromatography (HPLC) for drug analysis in different phases.Results showed that the recovery time in the atipamezole group was significantly shorter than control group (P<0.05)，values of HR were significantly higher than control group from 5 to 60 min after administration of atipamezole (P<0.05)，values of RR were significantly higher than control group from 10 to 15 min after administration of atipamezole (P<0.05)，the total scores of analgesia，sedation，skelaxin，posture，and auditory response were significantly higher than control group from 10 to 15 min after administration of atipamezole (P<0.05)，and pharmacokinetic parameters were as follows: T_1/2α was 11.0569±3.0934 min，T_1/2β was 875.421 8±159.375 3 min，AUC was 797 958.836 0±96 783.124 1 pg•(min•mL)^－1，T_peak was 9.544 0±0.484 4 min，C_max was 1 107.0652±121.620 1 pg•mL^－1.These results indicated that atipamezole is characterized by rapid drug action，slow metabolism，its best pharmacokinetic model was two-compartment open model，and atipamezole was effective for antagonizing the anaesthesia with XFM in minipigs.

中图分类号:

S859.791

姜胜，谭丽娟，李新，范宏刚，王洪斌. 小型猪专用复合麻醉剂麻醉后阿替美唑的颉颃效果及其体内药代动力学[J]. 畜牧兽医学报, 2014, 45(12): 2074-2080.

JIANG Sheng，TAN Li-juan，LI Xin，FAN Hong-gang，WANG Hong-bin. Antagonistic Effect of Atipamezole and Its Pharmacokinetics Following Anaesthesia with the Combined Anaesthetic for Miniature Pigs in Minipigs[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2014, 45(12): 2074-2080.

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参考文献

［1］LU D Z，FAN H G，KUN M，et al.Antagonistic effect of atipamezole，flumazenil and naloxone following anaesthesia with xylazine，tramadol and tiletamine/zolazepam combinations in pigs ［J］.Vet Anaesth Analg，2011，38(4)：301-309.
［2］VIRTANEN R，SAVOLA J M，SAANO V.Highly selective and specific antagonism of central and peripheral alpha 2-adrenoceptors by atipamezole ［J］.Arch Int Pharmacodyn Ther，1989，297：190-204.
［3］HAAPALINNA A，VIITAMAA T，MACDONALD E，et al.Evaluation of the effects of a specific α2-adrenoceptor antagonist，atipamezole，on α1-and α2-adrenoceptor subtype binding，brain neurochemistry and behaviour in comparison with yohimbine［J］.Naunyn Schmiedebergs Arch Pharmacol，1997，356(5)：570-582.
［4］PERTOVAARA A，HAAPALINNA A，SIRVIÖ J，et al.Pharmacological properties，central nervous system effects，and potential therapeutic applications of atipamezole，a selective alpha2-adrenoceptor antagonist ［J］.CNS Drug Rev，2005，11(3)：273-288.
［5］LU D Z，JIANG S，YU S M，et al.A Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam/xylazine and tiletamine-zolazepam/xylazine/tramadol in dogs ［J］.Pak Vet J，2014，34(1)：63-67.
［6］EWING K K，MOHAMMED H O，SCARLETT J M.Reduction of isoflurane anesthetic requirement by medetomidine and its restoration by atipamezole in dogs［J］.Am J Vet Res，1993，54(2)：294-299.
［7］JALANKA H.The use of medetomidine，medetomidine-ketamine combinations and atipamezole at Helsinki Zoo——a review of 240 cases ［J］.Acta Vet Scand Suppl，1989，85：193-197.
［8］尹柏双，石星星，李小波，等.阿替美唑对小型猪特异性麻醉剂诱导大鼠大脑皮质内Fos蛋白表达的影响［J］.畜牧兽医学报，2012，43(5)：821-825..
［9］范宏刚，卢德章，胡魁，等．小型猪复合麻醉剂对小型猪血流动力学及血浆中肾素-血管紧张素-醛固酮系统的影响［J］．畜牧兽医学报，2009，40（8）：1244-1248．
［10］SELMI A L，MENDES G M，FIGUEIREDO J P，et al.Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol［J］.Vet Anaesth Analg，2003，30(1)：24-29.
［11］王洪斌，李林林，谭丽娟，等．HPLC法测定小型猪血浆中阿替美唑含量的研究［J］．东北农业大学学报，2012，43（9）：32-36．
［12］PLUMB D C.Atipamezole［M］//Veterinary Drug Handbook.4^th ed.Ames，IA：Iowa State University Press.2002：76-77.
［13］SCHEININ H，MACDONALD E，SCHEININ M.Behavioural and neurochemical effects of antipamezole，a novel α₂-adrenoceptor antagonist［J］.Eur J Pharmacol，1988，151(1)：35-42.
［14］VIRTANEN R，SAVOLA J M，SAANO V.Highly selective and specific antagonism of central and peripheral α₂-adrenoceptors by atipamezole［J］.Arch Int Pharmacodyn Ther，1989，297：190-204.
［15］OROLA L，VEIDIS M V，MUTIKAINEN I，et al.The crystal and molecular structure of atipamezole base and atipamezole hydrochloride［J］.J Chem Crystallogr，2010，40(4)：302-305.

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小型猪专用复合麻醉剂麻醉后阿替美唑的颉颃效果及其体内药代动力学

Antagonistic Effect of Atipamezole and Its Pharmacokinetics Following Anaesthesia with the Combined Anaesthetic for Miniature Pigs in Minipigs

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