伊维菌素长效透皮剂和普通注射剂在家兔体内的药代动力学比较研究

doi:10.16431/j.cnki.1671-7236.2020.01.031

Abstract

Abstract: To compare the drug metabolism and efficacy time of ivermectin long-acting transdermal preparation and ordinary ivermectin injection,the study prepared the long-acting transdermal preparation with ivermectin content of 0.5%,1.0% and 1.5% respectively.The pharmacokinetics of ivermectin long-acting transdermal preparation and common ivermectin injection (1.0%) in rabbits with different dosage and the same volume were detected by HPLC,and the data were analyzed by PKSolver pharmacokinetic processing software.The results showed that the t_1/2ka of 0.5%,1.0%,1.5% ivermectin long-acting transdermal agent and 1.0% injection were 0.81,0.52,1.02 and 0.12 d,respectively;The T_max were 1.55,0.97,1.62 and 0.42 d,respectively;The C_max were 47.36,72.02,115.30,99.53 ng/mL,respectively;The t_1/2ke were 3.61,5.92,5.59 and 1.79 d;The MRT were 5.27,7.37,5.13 and 2.16 d,respectively;The AUC were 1 488.70,3 081.98,3 161.20 and 480.00 ng·d/mL,respectively.The effective concentration of long-acting transdermal agent of ivermectin was maintained for 35 d in vivo and 9 d in general injection.The effect of long-acting transdermal agents of ivermectin was confirmed,which could be further studied.

Key words: ivermectin; long-term transdermal agent; pharmacokinetic; HPLC

CLC Number:

S859.79⁺5

LIU Yingying, YUE Zhiguang, WU Ningpeng, LIU Zhenzhen, YAN Yaqun, ZHANG Sumei, JIAN Fuchun, ZHANG Longxian, WANG Rongjun, NING Changshen. Comparative Study on Pharmacokinetics of Long-acting Transdermal Agents of Ivermectin and Common Injection in Rabbits[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(1): 267-274.

References

[1] SATOSHI Q,CRUMP A.The life and times of ivermectin－A success story[J].Nature Reviews Microbiology,2004,2(12):984-989.
[2] CAMPBELL W C,FISHER M H,STAPLEY E O,et al.Ivermectin:A potent new antiparasitic agent[J].Science,1983,221(4613):823-828.
[3] PANAYOTOVA-PENCHEVA M S.Experience in the ivermectin treatment of internal parasites in zoo and captive wild animals:A review[J].Zoologische Garten,2016,85(5):280-308.
[4] 闻礼永,夏昭华,姚善滢,等.国产伊维菌素驱除犬钩虫、巴西日圆线虫、鼠蛲虫的效果[J].中国人兽共患病杂志,1999,15(1):27-29. WEN L Y,XIA Z H,YAO S Y,et al.Anthelmintic efficacy of national ivermectin on ancylostoma caninum,nippostrongylus brazilienses and syphacia mesocoriceti[J].Chinese Journal of Zoonoses,1999,15(1):27-29.(in Chinese)
[5] 吴仲达,李光裕,程霞,等.伊维菌素的驱虫应用研究进展[J].兽药与饲料添加剂,2002,7(2):21-23. WU Z D,LI G Y,CHENG X,et al.Advances in research on deworming application of ivermectin[J].Veterinary Pharmaceuticals & Feed Additives,2002,7(2):21-23.(in Chinese)
[6] 潘保良,蔡云鹏,张亚峰,等.伊维菌素在不同动物中安全性、药效学和药代动力学的差异性研究进展[J].中国兽药杂志,2018,52(5):75-81. PAN B L,CAI Y P,ZHANG Y F,et al.Research progress on the difference of safety,pharmacodynamics and pharmacokinetics of ivermectin in various animals[J].Chinese Journal of Veterinary Drug,2018,52(5):75-81.(in Chinese)
[7] LIFSCHITZ A,VIRKEL G,PIS A,et al.Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle[J].Veterinary Parasitology,1999,86(3):203-215.
[8] PEREZ R,CABEZASA I,GODOY C,et al.Pharmacokinetics of doramectin and ivermectin after oral administration in horses[J].Veterinary Journal,2002,163(2):161-167.
[9] GOKBULUT C,BOYACIOGLU M,KARADEMIR U.Plasma pharmacokinetics and faecal excretion of ivermectin (Eqvalan paste) and doramectin (Dectomax,1.0%) following oral administration in donkeys[J].Research in Veterinary Science,2005,79(3):233-238.
[10] 肖田安,怀彬彬,李帅鹏,等.伊维菌素PLA及PLGA微球混悬液在犬体内的药代动力学研究[J].华南农业大学学报,2014,35(3):8-12. XIAO T A,HUAI B B,LI S P,et al.Pharmacokinetics of ivermectin loaded PLA/PLGA microspheres suspension in dogs[J].Journal of South China Agricultural University,2014,35(3):8-12.(in Chinese)
[11] 王敏儒,陈杖榴.伊维菌素微球在家兔体内的药动学[J].畜牧兽医学报,2000,31(2):171-178. WANG M R,CHEN Z L.Pharmacokinetic properties of ivermectin loaded pla microspheres in rabbits[J].Chinese Journal of Animal and Veterinary Sciences,2000,31(2):171-178.(in Chinese)
[12] 张瑞丽,崔亮亮,郝智慧,等.5种伊维菌素注射液在家兔体内的比较药动学研究[J].中国畜牧兽医,2011,38(11):188-190. ZHANG R L,CUI L L,HAO Z H,et al.Compare pharmacokinetics of 5 different ivermectin injection in rabbit[J].China Animal Husbandry & Veterinary Medicine,2011,38(11):188-190.(in Chinese)
[13] 刘营营,岳治光,宁长申,等.伊维菌素长效透皮剂的研制及含量测定[J].河南农业科学,2018,47(2):130-134. LIU Y Y,YUE Z G,NING C S,et al.Preparation and content determination of long-acting transdermal agent of ivermectin[J].Journal of Henan Agricultural Sciences,2018,47(2):130-134.(in Chinese)
[14] 孙雪峰,张要齐,许贤会,等.阿维菌素纳米脂质体在山羊体内的药动学研究[J].动物医学进展,2014,35(10):71-74. SUN X F,ZHANG Y Q,XU X H,et al.Study on pharmacokinetics of ivermectin nanometre liposomes in goats[J].Progress in Veterinary Medicine,2014,35(10):71-74.(in Chinese)
[15] TUMIPSEED S B,ROYBAL J E,ANDERSEN W C,et al.Analysis of avermectin and moxidectin residues in milk by liquid chromatography-tandem mass spectrometry using an atmospheric pressure chemical ionization/atmospheric pressure photoionization source[J].Analytica Chimica Acta,2005,529(1-2):159-165.
[16] HSIEH J Y K,LIN L,FANG W,et al.Robotic sample preparation and HPLC determination of the major component of ivermectin in human plasma[J].Journal of Liquid Chromatography & Related Technologies,2003,26(6):895-910.
[17] CPOLLMEIER M,MAIER S,MORIARTY K,et al.High-performance liquid chromatographic assay for the determination of a semisynthetic avermectin analog (eprinomectin) in bovine milk at parts per billion levels——Method development and validation[J].Journal of Chromatography B,2002,772(1):99-105.
[18] 周红蕾,刘仁杰,汤仁想,等.高效液相色谱荧光检测法检测Beagle犬血浆中伊维菌素的试验[J].中国兽医杂志,2014,50(3):78-81. ZHOU H L,LIU R J,TANG R X,et al.Detection of ivermectin in Beagle dog plasma by HPLC fluorescence detection[J].Chinese Journal of Veterinary Medicine,2014,50(3):78-81.(in Chinese)
[19] 文豪.伊维菌素微乳在羊体内的药代动力学与残留研究[D].北京:中国农业科学院,2016. WEN H.The pharmacokinetics and residue of ivermectin microemulsion in sheep[D].Beijing:Chinese Academy of Agricultural Sciences,2016.(in Chinese)
[20] 斯奈德L R,柯克兰J J.现代液相色谱法导论[M].北京:化学工业出版社,1980. SNYDET L R,KIEKLAND J J.Introduction to Modern Liquid Chromatography (MySQL)[M].Beijing:Chemical Industry Press,1980.(in Chinese)
[21] 王嗣涵,张继瑜,邢守叶,等.伊维菌素微乳中伊维菌素的含量测定方法研究[J].中国畜牧兽医,2017,44(6):1861-1868. WANG S H,ZHANG J Y,XING S Y,et al.Content determination of ivermectin in the ivermectin microemulsion injection.[J].China Animal Husbandry & Veterinary Medicine,2017,44(6):1861-1868.(in Chinese)
[22] ALOUT H,FOY B.Ivermectin:A complimentary weapon against the spread of malaria?[J].Expert Review of Anti-Infective Therapy,2016,15(3):231-240.
[23] SAMPAIO V S,BELTRAN T P,KOBYLINSKI K C,et al.Filling gaps on ivermectin knowledge:Effects on the survival and reproduction of Anopheles aquasalis,a Latin American malaria vector[J].Malaria Journal,2016,15(1):491.
[24] 胡颖.伊维菌素聚乳酸纳米粒的初步研究[D].杨凌:西北农林科技大学,2008. HU Y.Preliminary study on ivermectin polylactic acid nanoparticles[D].Yangling:Northwest A & F University,2008.(in Chinese)
[25] 陈博.复方伊维菌素干混悬剂制备及其在大鼠体内代谢特征分析[D].哈尔滨:东北农业大学,2019. CHEN B.Preparation of compound ivermectin dry suspension and analysis of its metabolic characteristics in rats[D].Harbin:Northeast Agricultural University,2019.(in Chinese)
[26] 任丽君,郭玉娟,姚军,等.伊维菌素缓释注射液的制备工艺及在绵羊体内药代动力学研究[J].西北药学杂志,2016,31(5):497-500. REN L J,GUO Y J,YAO J,et al.Study on preparation technology and pharmacokinetics of ivermectin sustained release injection in sheep[J].Northwest Pharmaceutical Journal,2016,31(5):497-500.(in Chinese)
[27] 徐霞.伊维菌素脂质体的毒理学、药动学及对猪疥螨病疗效的研究[D].长沙:湖南农业大学,2006. XU X.Studies on the toxicology,pharmacokinetic of ivermectin liposomes and its therapeutic effect on scabies mange[D].Changsha:Hunan Agricultural University,2006.(in Chinese)

Comparative Study on Pharmacokinetics of Long-acting Transdermal Agents of Ivermectin and Common Injection in Rabbits

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	YANG Yuxin, ZHAO Fuhua, LIU Yu, QIU Jicheng, CAO Yuying, ZHANG Lu, BAI Runian, WANG Jianzhong, CAO Xingyuan. Pharmacokinetics and Bioequivalence of Two Cephalexin Formulations in Beagle Dogs [J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(1): 386-394.
[2]	PU Shanju, HUANG Lingli, MI Kun, SUN Da, WANG Hanyu, PAN Yuanhu, LIU Zhenli. Comparative Pharmacokinetics of Ceftiofur Hydrochloride Injection in Pigs [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(4): 1472-1481.
[3]	GENG Xiang, LIU Xiwang, YANG Yajun, LI Jianyong. Establishment of HPLC Method for Determination of Eprinomectin and Related Substances in Eprinomectin Sustained-release Injection [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(12): 4681-4689.
[4]	ZHANG Le, ZHANG Guangfeng, ZHU Chongmiao, WU Zhi, ZHU Shanyuan, YU Shenglan, FENG Qi, XING Xiaoling, ZHAO Qiannan. Study on Pharmacokinetics of Cyclodextrin-encapsulated Flufenicol in Pigs [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(6): 1934-1941.
[5]	HAN Yiqing, JI Xun, CHEN Chunqin, LIU Mingjiang, LI Jingui. Study on the Metabolism of Artemisinin in Chickens by LC-MS/MS [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(9): 2778-2786.
[6]	SHI Feifei, WANG Jing, QIN Feng, CHEN Xiaolan, GAO Jianru, WEI Yu, ZHANG Long. Study on Pharmacokinetics of a Novel Veterinary Nanoemulsion Drug Loading System in Rats [J]. , 2019, 46(4): 1236-1243.
[7]	LI Xiaoting, BAI Yubin, LI Bing, DONG Zhen, SUN Jichao, CHENG Fusheng, ZHANG Jiyu. Determination of Related Substances in Oxyclozanide and Albendazole Compound Suspension by HPLC [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3422-3431.
[8]	JIANG Zhihui, ZHANG Jingmiao, QU Yicheng, ZHANG Shouquan, CHANG Xuemei, GUO Xiao. Effect of Essential Oil from Artemisia vulgaris on CYP450 Isoforms Activity and Expression [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3440-3448.
[9]	LI Mei, SUN Lingling, YUAN Zonghui, HUANG Lingli. Research Progress on Veterinary Cephalosporins [J]. , 2018, 45(7): 1978-1989.
[10]	LI Jiao, LI Qingshan, XU Fengbo. Research Progress of Moxidectin in Animal Husbandry [J]. , 2018, 45(12): 3587-3593.
[11]	LI Peng, YANG Xin, MIAO Hong, LI Jingguang, ZHAO Yunfeng, WU Yongning. Simultaneous Determination of 8 Triazine Pesticides in Milk and Dairy Products from Total Diet by Isotope Dilution-High Performance Liquid Chromatography-Linear Ion Trap Mass Spectrometry [J]. , 2018, 45(10): 2960-2968.
[12]	LI Lei-ting, LIU Jun-hua, LIU Bao-tao, FU Hong-lei, ZOU Ming. Residue Analysis of Five Kinds of Penicillins in Eggs by High Performance Liquid Chromatography-Ultraviolet Detection [J]. , 2017, 44(8): 2483-2488.
[13]	SAN Ren, BA La, YUE Wei-dong, HASI Su-rong. Determination of Acetaminophen in Bactrian Camel Plasma by RP-HPLC [J]. , 2017, 44(8): 2517-2522.
[14]	ZHENG Yi, CHEN Xiao-lan, GUAN Yuan-hong, JIA Ji-ping, YANG Hai-feng, LI Shi-yang, LI Ran. Determination of Pinoresinol Diglucoside in Eucommie ulmoides Immunoenhancement Liquids by RP-HPLC [J]. , 2017, 44(7): 2197-2202.
[15]	WANG Si-han, ZHANG Ji-yu, XING Shou-ye, LI Bing, ZHOU Xu-zheng. Content Determination of Ivermectin in the Ivermectin Microemulsion Injection [J]. , 2017, 44(6): 1861-1868.