莫西菌素在畜牧业中的应用研究进展
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摘要
莫西菌素(moxidectin,MOX)是由链霉菌发酵产生的奈马菌素经衍生化得到,具有良好的驱虫活性且对哺乳动物安全,主要应用于畜牧业。莫西菌素相较于其他阿维菌素类药物具有更好的脂溶性和水溶性,在动物体内脂肪组织中分布最高。莫西菌素通过与γ-氨基丁酸(GABA)结合,使Cl-大量内流造成神经膜电位超极化,导致虫体麻痹死亡。给药途径和动物生理状况的不同会影响其峰血浆浓度和药物半衰期。莫西菌素在牛、羊、犬等动物体内具有很好的驱虫活性,其应用范围从哺乳动物逐渐扩展到鸟类,防治对象从线虫逐渐扩展到螨虫和部分病原菌,研究方向也从驱虫活性延伸至治疗人类疾病。随着莫西菌素应用范围的扩大和时间的延长,耐药性开始出现,可以采用莫西菌素和其他药剂混合等方式降低耐药性的产生速度。探究其更广泛的作用,需要不同研究领域研究人员的共同努力。
Moxidectin(MOX)is derived from derivatization of nemadectin produced by Streptomyces(Cyanneogrisens noncyanogenus),which has good insect repellent activity and is safe for mammals,and it is mainly used in animal husbandry.Moxidectin has better fat-soluble and watersoluble than other avermectin drugs,and has the highest distribution in adipose tissues of animals.Moxidectin binds to GABA,and neural membrane potential hyperpolarization is caused by massive influx of Cl-,resulting in the death due to the insect's body paralysis.Differences in the route of administration and the physiological condition of animals would affect the peak concentration and depletion half-lives.Moxidectin has good insect repellent activity in animals such as cattle,sheep and dogs.The application range of moxidectin gradually expands from mammals to birds,and the control objects gradually extend from nematodes to mite and several kinds of germs.The research direction extends from anthelmintic activity to the treatment of human diseases.With the increase of the application range of moxidectin and the prolongation of time,the drug resistance began to appear,and the rate of drug resistance could be reduced by the combination of moxidectin and other agents.Exploring the wider role of moxidectin requires the efforts of researchers in different fields.
Moxidectin(MOX)is derived from derivatization of nemadectin produced by Streptomyces(Cyanneogrisens noncyanogenus),which has good insect repellent activity and is safe for mammals,and it is mainly used in animal husbandry.Moxidectin has better fat-soluble and watersoluble than other avermectin drugs,and has the highest distribution in adipose tissues of animals.Moxidectin binds to GABA,and neural membrane potential hyperpolarization is caused by massive influx of Cl-,resulting in the death due to the insect's body paralysis.Differences in the route of administration and the physiological condition of animals would affect the peak concentration and depletion half-lives.Moxidectin has good insect repellent activity in animals such as cattle,sheep and dogs.The application range of moxidectin gradually expands from mammals to birds,and the control objects gradually extend from nematodes to mite and several kinds of germs.The research direction extends from anthelmintic activity to the treatment of human diseases.With the increase of the application range of moxidectin and the prolongation of time,the drug resistance began to appear,and the rate of drug resistance could be reduced by the combination of moxidectin and other agents.Exploring the wider role of moxidectin requires the efforts of researchers in different fields.
引文
[1] HIDALGO-ARGELLO M R,DEZ-BAOS N,ROJO-VZQUEZ F A.Efficacy of moxidectin 1%injectable and 0.2%oral drench against natural infection by Dictyocaulus filaria in sheep[J].Veterinary Parasitology,2002,107(1-2):95-101.
[2]刘开永,李英伦,周岷江.驱虫抗生素莫西菌素的研究应用进展[J].兽药与饲料添加剂,2003,8(4):13-16.LIU K Y,LI Y L,ZHOU M J.Progress in research and application of moxidectin as an anthelmintic antibiotic[J].Veterinary Drugs and Feed Additives,2003,8(4):13-16.(in Chinese)
[3]郑小莉,林仙军.莫西菌素在养殖业中的应用与研究[J].浙江畜牧兽医,2014,39(1):21-22.ZHENG X L,LIN X J.Application and research of moxidectin in animal husbandry[J].Zhejiang Animal Husbandry and Veterinary,2014,39(1):21-22.(in Chinese)
[4]刘开永,李英伦,周岷江.新一代驱虫抗生素——莫西菌素[J].动物医学进展,2003,24(4):59-62.LIU K Y,LI Y L,ZHOU M J.A new generation of anthelmintic antibiotics—Moxidectin[J].Progress in Animal Medicine,2003,24(4):59-62.(in Chinese)
[5] LIFCHITZ A,VIRKEL G,SALLOVITZ J,et al.Loperamide-induced enhancement of moxidectin availability in cattle[J].Journal of Veterinary Pharmacology and Therapeutics,2002,25(2):111-120.
[6] MCKELLAR Q A,BENCHAOUI H A.Avermectins and milbemycins[J].Journal of Veterinary Pharmacology and Therapeutics,1996,19(5):311-351.
[7] LESPINE A,DUPUY J,ORLOWSKI S,et al.Interaction of ivermectin with multidrug resistance proteins(MRP1,2and 3)[J].Chemico-Biological Interactions,2006,159(3):169-179.
[8] LESPINE A,MARTIN S,DUPUY J,et al.Interaction of macrocyclic lactones with P-glycoprotein:Structure-affinity relationship[J].European Journal of Pharmaceutical Sciences Official Journal of the European Federation for Pharmaceutical Sciences,2007,30(1):84-94.
[9] PAUL A J,TRANQUILLI W J,HUTCHENS D E.Safety of moxidectin in avermectin-sensitive collies[J].American Journal of Veterinary Research,2000,61(5):482-483.
[10] BYGARSKI E E,PRICHARD R K,ARDELLI B F.Resistance to the macrocyclic lactone moxidectin is mediated in part by membrane transporter P-glycoproteins:Implications for control of drug resistant parasitic nematodes[J].International Journal for Parasitology:Drugs and Drug Resistance,2014,4(3):143-151.
[11] LEE V K,TIWARY A K,SHARMA-REDDY P,et al.Moxidectin toxicity in senescence-accelerated prone and resistant mice[J].Comparative Medicine,2009,59(3):227-233.
[12] AFZAL J,STOUT S J,DACUNHA A R,et al.Moxidectin:Absorption,tissue distribution,excretion,and biotransformation of 14C-labeled moxidectin in sheep[J].Journal of Agricultural and Food Chemistry,1994,42(8):1767-1773.
[13] ZULALIAN J,STEVEN J S,ADRIAN R,et al.Absorption,tissue distribution,metabolism and excretion of moxidection in cattle[J].Journal of Agricultural and Food Chemistry,1994,42(2):381-387.
[14] DEL M B A C,FERNANDES M,DE P C B,et al.Moxidectin residues in lamb tissues:Development and validation of analytical method by UHPLC-MS/MS[J].Journal of Chromatography B,2018,1072:390-396.
[15] LIFSCHITZ A,IMPERIALE F,VIRKEL G,et al.Depletion of moxidectin tissue residues in sheep[J].Journal of Agricultural and Food Chemistry,2000,48(12):6011-6015.
[16] COCQUYT C M,VAN A S,COX S,et al.Pharmacokinetics of moxidectin in alpacas following administration of an oral or subcutaneous formulation[J].Research in Veterinary Science,2016,105:160-164.
[17] CRAVEN J,BJRN H,HENNESSY D R.et al.The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs[J].Journal of Veterinary Pharmacology and Therapetics,2002,25(3):227-232.
[18] RODRGUEZ-VIVAS R,CASTILLOCHAB C G,ROSADOAGUILAR J,et al.Evaluation of the efficacy and persistence of moxidectin(10%)and ivermectin(3.15%)against natural infestation of gastrointestinal nematodes in cattle from the Mexican tropics[J].Archivos De Medicina Veterinaria,2014,46(1):69-74.
[19] GEURDEN T,CHARTIER C,FANKE J,et al.Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe[J].International Journal for Parasitology:Drugs and Drug Resistance,2015,5(3):163-171.
[20] FAZZIO L E,STREITENBERGER N,GALVAN W R,et al.Efficacy and productive performance of moxidectin in feedlot calves infected with nematodes resistant to ivermectin[J].Veterinary Parasitology,2016,223:26-29.
[21] VADLEJCH J,MAKOVICH Y'P,CˇADKOVZ,et al.Efficacy and persistent activity of moxidectin against natural Muelleriuscapillaris,infection in goats and pathological consequences of muelleriosis[J].Veterinary Parasitology,2016,218:98-101.
[22] RAGBETLI C,CEYLAN E,TANRITANIR P.The efficacy of moxidectin against gastrointestinal nematode infections in goats[J].Asian Journal of Animal and Veterinary Advances,2009,4(3):134-138.
[23] PITTERNA T,CASSAYRE J,HTER O F,et al.New ventures in the chemistry of avermectins[J].Bioorganic and Medicinal Chemistry,2009,17(12):4085-4095.
[24] OTRANTO D,COLELLA V,CRESCENZO G,et al.Efficacy of moxidectin 2.5%and imidacloprid 10%in the treatment of ocular thelaziosis by Thelazia callipaedain naturally intected dogs[J].Veterinary Parasitology,2016,227:118-121.
[25] BECSKEI C,BOCK F D,ILLAMBAS J,et al.Efficacy and safety of a novel oral isoxazoline,sarolaner(SimparicaTM),for the treatment of sarcoptic mange in dogs[J].Veterinary Parasitology,2016,222(56):56-61.
[26] REGALNONO A F D,CESARE A D,TRAVERSA D,et al.Microfilaricidal efficacy of a single administration of Advocate(Bayer Animal Health)in dogs naturally infected with Dirofilaria immitis,or Dirofilaria repens[J].Veterinary Parasitology,2016,226:30-34.
[27] BOUSSINESQ M.A new powerful drug to combat river blindness[J].Lancet,2018,392(10154):1170-1172.
[28] OPOKU N O,BAKAJIKA D K,KANZA E M,et al.Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana,Liberia,and the Democratic Republic of the Congo:A randomised,controlled,double-blind phase 3 trial[J].Lancet,2018,392(10154):1207-1216.
[29] BERNIGAUD C,FANG F,FISCHER K,et al.Preclinical study of single-dose moxidectin,a new oral treatment for scabies;Efficacy,safety,and pharmacokinetic compared to two-dose ivermectin in a porcine model[J].PLoS Neglected Tropical Diseases,2016,10(10):e0005030.
[30] HAN H S,NOLI C,CENA T.Efficacy and duration of oral fluralaner and spot-on moxidectin/imidacloprid in cats infested with Lynxacarus radovskyi[J].Veterinary Dermatology,2016,27(6):474-e127.
[31] KIM K R,AHN K S,OH D S,et al.Efficacy of a combination of 10%imidacloprid and 1%moxidectin against Caparinia tripilis in African pygamy hedgehog(Atelerix albiventris)[J].Parasites and Vectors,2012,5(1):158.
[32]韦冬妹,王先坤,唐得淋,等.多拉菌素和莫西菌素治疗鸡体内犬蛔虫幼虫试验[A].中国畜牧兽医学会兽医寄生虫学分会第十三次学术研讨会论文集[C].2015.WEI D M,WANG X K,TANG D L,et al.Test of canine larvae in chickens with doramectin and moxidectin[A].Chinese Society of Animal Husbandry and Veterinary Sciences Veterinary Parasitology 13th Symposium Proceedings[C].2015.(in Chinese)
[33] SOUZA L P D,LELIS R T,GRANJA I R A,et al.Efficacy of albendazole and moxidectin and resistance to ivermectin against Libyosstrongylust douglassil and Libyostrongylus denstatus in ostriches[J].Veterinary Parasitologly,2012,189(2-4):387-389
[34] HUYNH N,ARABIAN N,NAITO A,et al.Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder[J].Neuropharmacology,2017,113(Pt A):60-70.
[35] ELGHRYANI N,WAAL T D.Anthelmintic resistance in Irish equine nematode populations[J].Journal of Equine Veterinary Science,2016,39:S55.
[36] DANIELS S P,PROUDMAN C J.Shortened egg reappearance after ivermectin or moxidectin use in horses in the UK[J].Veterinary Journal,2016,218:36-39.
[37] RAMOS F,PORTELLA L P,RODRIGUES F D S,et al.Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul,Brazil[J].International Journal for Parasitology:Drugs and Drug Resistance,2016,6(1):93-101.
[2]刘开永,李英伦,周岷江.驱虫抗生素莫西菌素的研究应用进展[J].兽药与饲料添加剂,2003,8(4):13-16.LIU K Y,LI Y L,ZHOU M J.Progress in research and application of moxidectin as an anthelmintic antibiotic[J].Veterinary Drugs and Feed Additives,2003,8(4):13-16.(in Chinese)
[3]郑小莉,林仙军.莫西菌素在养殖业中的应用与研究[J].浙江畜牧兽医,2014,39(1):21-22.ZHENG X L,LIN X J.Application and research of moxidectin in animal husbandry[J].Zhejiang Animal Husbandry and Veterinary,2014,39(1):21-22.(in Chinese)
[4]刘开永,李英伦,周岷江.新一代驱虫抗生素——莫西菌素[J].动物医学进展,2003,24(4):59-62.LIU K Y,LI Y L,ZHOU M J.A new generation of anthelmintic antibiotics—Moxidectin[J].Progress in Animal Medicine,2003,24(4):59-62.(in Chinese)
[5] LIFCHITZ A,VIRKEL G,SALLOVITZ J,et al.Loperamide-induced enhancement of moxidectin availability in cattle[J].Journal of Veterinary Pharmacology and Therapeutics,2002,25(2):111-120.
[6] MCKELLAR Q A,BENCHAOUI H A.Avermectins and milbemycins[J].Journal of Veterinary Pharmacology and Therapeutics,1996,19(5):311-351.
[7] LESPINE A,DUPUY J,ORLOWSKI S,et al.Interaction of ivermectin with multidrug resistance proteins(MRP1,2and 3)[J].Chemico-Biological Interactions,2006,159(3):169-179.
[8] LESPINE A,MARTIN S,DUPUY J,et al.Interaction of macrocyclic lactones with P-glycoprotein:Structure-affinity relationship[J].European Journal of Pharmaceutical Sciences Official Journal of the European Federation for Pharmaceutical Sciences,2007,30(1):84-94.
[9] PAUL A J,TRANQUILLI W J,HUTCHENS D E.Safety of moxidectin in avermectin-sensitive collies[J].American Journal of Veterinary Research,2000,61(5):482-483.
[10] BYGARSKI E E,PRICHARD R K,ARDELLI B F.Resistance to the macrocyclic lactone moxidectin is mediated in part by membrane transporter P-glycoproteins:Implications for control of drug resistant parasitic nematodes[J].International Journal for Parasitology:Drugs and Drug Resistance,2014,4(3):143-151.
[11] LEE V K,TIWARY A K,SHARMA-REDDY P,et al.Moxidectin toxicity in senescence-accelerated prone and resistant mice[J].Comparative Medicine,2009,59(3):227-233.
[12] AFZAL J,STOUT S J,DACUNHA A R,et al.Moxidectin:Absorption,tissue distribution,excretion,and biotransformation of 14C-labeled moxidectin in sheep[J].Journal of Agricultural and Food Chemistry,1994,42(8):1767-1773.
[13] ZULALIAN J,STEVEN J S,ADRIAN R,et al.Absorption,tissue distribution,metabolism and excretion of moxidection in cattle[J].Journal of Agricultural and Food Chemistry,1994,42(2):381-387.
[14] DEL M B A C,FERNANDES M,DE P C B,et al.Moxidectin residues in lamb tissues:Development and validation of analytical method by UHPLC-MS/MS[J].Journal of Chromatography B,2018,1072:390-396.
[15] LIFSCHITZ A,IMPERIALE F,VIRKEL G,et al.Depletion of moxidectin tissue residues in sheep[J].Journal of Agricultural and Food Chemistry,2000,48(12):6011-6015.
[16] COCQUYT C M,VAN A S,COX S,et al.Pharmacokinetics of moxidectin in alpacas following administration of an oral or subcutaneous formulation[J].Research in Veterinary Science,2016,105:160-164.
[17] CRAVEN J,BJRN H,HENNESSY D R.et al.The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs[J].Journal of Veterinary Pharmacology and Therapetics,2002,25(3):227-232.
[18] RODRGUEZ-VIVAS R,CASTILLOCHAB C G,ROSADOAGUILAR J,et al.Evaluation of the efficacy and persistence of moxidectin(10%)and ivermectin(3.15%)against natural infestation of gastrointestinal nematodes in cattle from the Mexican tropics[J].Archivos De Medicina Veterinaria,2014,46(1):69-74.
[19] GEURDEN T,CHARTIER C,FANKE J,et al.Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe[J].International Journal for Parasitology:Drugs and Drug Resistance,2015,5(3):163-171.
[20] FAZZIO L E,STREITENBERGER N,GALVAN W R,et al.Efficacy and productive performance of moxidectin in feedlot calves infected with nematodes resistant to ivermectin[J].Veterinary Parasitology,2016,223:26-29.
[21] VADLEJCH J,MAKOVICH Y'P,CˇADKOVZ,et al.Efficacy and persistent activity of moxidectin against natural Muelleriuscapillaris,infection in goats and pathological consequences of muelleriosis[J].Veterinary Parasitology,2016,218:98-101.
[22] RAGBETLI C,CEYLAN E,TANRITANIR P.The efficacy of moxidectin against gastrointestinal nematode infections in goats[J].Asian Journal of Animal and Veterinary Advances,2009,4(3):134-138.
[23] PITTERNA T,CASSAYRE J,HTER O F,et al.New ventures in the chemistry of avermectins[J].Bioorganic and Medicinal Chemistry,2009,17(12):4085-4095.
[24] OTRANTO D,COLELLA V,CRESCENZO G,et al.Efficacy of moxidectin 2.5%and imidacloprid 10%in the treatment of ocular thelaziosis by Thelazia callipaedain naturally intected dogs[J].Veterinary Parasitology,2016,227:118-121.
[25] BECSKEI C,BOCK F D,ILLAMBAS J,et al.Efficacy and safety of a novel oral isoxazoline,sarolaner(SimparicaTM),for the treatment of sarcoptic mange in dogs[J].Veterinary Parasitology,2016,222(56):56-61.
[26] REGALNONO A F D,CESARE A D,TRAVERSA D,et al.Microfilaricidal efficacy of a single administration of Advocate(Bayer Animal Health)in dogs naturally infected with Dirofilaria immitis,or Dirofilaria repens[J].Veterinary Parasitology,2016,226:30-34.
[27] BOUSSINESQ M.A new powerful drug to combat river blindness[J].Lancet,2018,392(10154):1170-1172.
[28] OPOKU N O,BAKAJIKA D K,KANZA E M,et al.Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana,Liberia,and the Democratic Republic of the Congo:A randomised,controlled,double-blind phase 3 trial[J].Lancet,2018,392(10154):1207-1216.
[29] BERNIGAUD C,FANG F,FISCHER K,et al.Preclinical study of single-dose moxidectin,a new oral treatment for scabies;Efficacy,safety,and pharmacokinetic compared to two-dose ivermectin in a porcine model[J].PLoS Neglected Tropical Diseases,2016,10(10):e0005030.
[30] HAN H S,NOLI C,CENA T.Efficacy and duration of oral fluralaner and spot-on moxidectin/imidacloprid in cats infested with Lynxacarus radovskyi[J].Veterinary Dermatology,2016,27(6):474-e127.
[31] KIM K R,AHN K S,OH D S,et al.Efficacy of a combination of 10%imidacloprid and 1%moxidectin against Caparinia tripilis in African pygamy hedgehog(Atelerix albiventris)[J].Parasites and Vectors,2012,5(1):158.
[32]韦冬妹,王先坤,唐得淋,等.多拉菌素和莫西菌素治疗鸡体内犬蛔虫幼虫试验[A].中国畜牧兽医学会兽医寄生虫学分会第十三次学术研讨会论文集[C].2015.WEI D M,WANG X K,TANG D L,et al.Test of canine larvae in chickens with doramectin and moxidectin[A].Chinese Society of Animal Husbandry and Veterinary Sciences Veterinary Parasitology 13th Symposium Proceedings[C].2015.(in Chinese)
[33] SOUZA L P D,LELIS R T,GRANJA I R A,et al.Efficacy of albendazole and moxidectin and resistance to ivermectin against Libyosstrongylust douglassil and Libyostrongylus denstatus in ostriches[J].Veterinary Parasitologly,2012,189(2-4):387-389
[34] HUYNH N,ARABIAN N,NAITO A,et al.Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder[J].Neuropharmacology,2017,113(Pt A):60-70.
[35] ELGHRYANI N,WAAL T D.Anthelmintic resistance in Irish equine nematode populations[J].Journal of Equine Veterinary Science,2016,39:S55.
[36] DANIELS S P,PROUDMAN C J.Shortened egg reappearance after ivermectin or moxidectin use in horses in the UK[J].Veterinary Journal,2016,218:36-39.
[37] RAMOS F,PORTELLA L P,RODRIGUES F D S,et al.Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul,Brazil[J].International Journal for Parasitology:Drugs and Drug Resistance,2016,6(1):93-101.