牦牛主要寄生虫病高效低残留防治技术研究(中)
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摘要
为制定埃普利诺菌素(EPR)休药期及建立牦牛主要寄生虫病高效低残留防治技术提供科学依据。采用荧光高效液相色谱法(HPLC-FLD)检测埃普利诺菌素(EPR)注射剂在牦牛奶中的残留消除规律。结果表明:给泌乳牦牛皮下注射EPR注射液0.2mg·kg~(-1)剂量,EPR在牛奶中分布浓度较低,在给药后54.00h,牛奶中的EPR浓度达到峰值7.38±2.61ng·mL~(-1),该值低于美国规定的EPR在牛奶中的最高残留限量(12ng·mL~(-1))和欧盟及联合国粮食与农业组织(FAO)规定的EPR在牛奶中的最高残留限量(20ng·mL~(-1))。给泌乳牦牛皮下注射EPR注射液0.4mg·kg~(-1)剂量,EPR在牛奶中分布浓度较低,在给药后42.00 h,牛奶中的EPR浓度达到峰值8.42±4.62 ng·mL~(-1),最高值低于欧盟和联合国粮食与农业组织(FAO)规定的EPR在牛奶中的最高残留限量(20ng·mL~(-1)),略高于美国规定的EPR在牛奶中的最高残留限量(12ng·mL~(-1));在给药后56.00 h,牛奶中的EPR浓度达到峰值6.98±2.98 ng·mL~(-1),该值低于美国规定的EPR在牛奶中的最高残留限量(12ng·mL~(-1))和欧盟及联合国粮食与农业组织(FAO)规定的EPR在牛奶中的最高残留限量(20ng·mL~(-1))。国产药物试验组与进口商品化制剂对照组的两种EPR浇泼剂在牦牛血浆中的残留消除规律,分别于1.67±0.2d与1.83±0.61d(Tmax)在血浆中达到最高药物浓度(Cmax)7.88±2.68ng·mL~(-1)与5.94±2.80ng·mL~(-1),两种EPR制剂的生物等效性无显著性差异。国产和进口两种制剂的残留均低于联合国粮食与农业组织(FAO)所规定的最高残留限量(20ng·mL~(-1))。研究结果表明,EPR注射剂0.2mg·kg~(-1)、0.4mg·kg~(-1),EPR浇泼剂0.5mg·kg~(-1)推荐剂量用于泌乳牦牛无需弃奶期,牦牛乳用时无需休药期或建议休药期为1d。为建立牦牛主要寄生虫病高效低残留防治技术提供了依据。
To provide scientific basis for the formulation of EPR in withdrawal period and the establishment of effective and low residue control technology for main parasitic diseases of yak. Fluorescence high performance liquid chromatography(HPLC-FLD) was used to detect the residual elimination rule of EPR injection agent in yak milk. The results showed that after the subcutaneous injection of 0.2 mg·Kg~(-1) dose of EPR into lactating yaks, the concentration of EPR in milk was relatively low, and reached a peak of 7.38±2.61 ng·mL~(-1)at 54.00 h after administration, which was lower than the maximum residue limit of EPR(20ng. mL~(-1)) in milk stipulated by the European Union and the maximum residue limit of EPR(12ng·mL~(-1)) in milk stipulated by the United States. After the subcutaneous injection of 0.4 mg·Kg~(-1) dose of EPR into lactating yaks, the concentration of EPR in milk was relatively low. The concentration of EPR in milk reached a peak of 8.42± 4.62 ng·mL~(-1) at 42.00 h, which was slightly higher than the maximum residue limit of EPR(20ng. mL~(-1)) in milk stipulated by the United States. At 56.00 h after administration, the concentration of EPR in milk reached the peak value of 6.98 ±2.98 ng..mL~(-1).This value is lower than the maximum residue limit(12ng·mL~(-1)) of EPR in milk stipulated by the United States and the maximum residue limit(20 ng·mL~(-1)) of EPR in milk stipulated by the European Union. The residual elimination of the two EPR agents in yak plasma for the domestic drug test group and the foreign commercial preparation control group reached the maximum drug concentration of 7.88±2.68 ng·mL~(-1) and 5.94±2.80 ng·mL~(-1) in plasma at 1.67 ±0.2 d and 1.83± 0.61 d, respectively. There was no significant difference in the bioequivalence between the two EPR preparations. The results showed that EPR injection 0.2 mg. Kg ~(-1), 0.4 mg. Kg ~(– 1) andEPR pouring 0.5 mg Kg ~(-1) were used for lactation yak, milk without having to abandon, for milk stage is with no need for withdrawal period or suggest 1 d withdrawal period. It provides a basis for the establishment of effective and low residue control technology of main parasitic diseases of yak.
To provide scientific basis for the formulation of EPR in withdrawal period and the establishment of effective and low residue control technology for main parasitic diseases of yak. Fluorescence high performance liquid chromatography(HPLC-FLD) was used to detect the residual elimination rule of EPR injection agent in yak milk. The results showed that after the subcutaneous injection of 0.2 mg·Kg~(-1) dose of EPR into lactating yaks, the concentration of EPR in milk was relatively low, and reached a peak of 7.38±2.61 ng·mL~(-1)at 54.00 h after administration, which was lower than the maximum residue limit of EPR(20ng. mL~(-1)) in milk stipulated by the European Union and the maximum residue limit of EPR(12ng·mL~(-1)) in milk stipulated by the United States. After the subcutaneous injection of 0.4 mg·Kg~(-1) dose of EPR into lactating yaks, the concentration of EPR in milk was relatively low. The concentration of EPR in milk reached a peak of 8.42± 4.62 ng·mL~(-1) at 42.00 h, which was slightly higher than the maximum residue limit of EPR(20ng. mL~(-1)) in milk stipulated by the United States. At 56.00 h after administration, the concentration of EPR in milk reached the peak value of 6.98 ±2.98 ng..mL~(-1).This value is lower than the maximum residue limit(12ng·mL~(-1)) of EPR in milk stipulated by the United States and the maximum residue limit(20 ng·mL~(-1)) of EPR in milk stipulated by the European Union. The residual elimination of the two EPR agents in yak plasma for the domestic drug test group and the foreign commercial preparation control group reached the maximum drug concentration of 7.88±2.68 ng·mL~(-1) and 5.94±2.80 ng·mL~(-1) in plasma at 1.67 ±0.2 d and 1.83± 0.61 d, respectively. There was no significant difference in the bioequivalence between the two EPR preparations. The results showed that EPR injection 0.2 mg. Kg ~(-1), 0.4 mg. Kg ~(– 1) andEPR pouring 0.5 mg Kg ~(-1) were used for lactation yak, milk without having to abandon, for milk stage is with no need for withdrawal period or suggest 1 d withdrawal period. It provides a basis for the establishment of effective and low residue control technology of main parasitic diseases of yak.
引文
[1] 青海省畜牧厅主编.青海省畜禽疫病志[M].兰州:甘肃人民出版社.1993:196-297.
[2] 殷铭阳,周东辉,刘建枝,等.中国牦牛主要寄生虫病流行现状及防控策略[J].中国畜牧兽医,2014,(5):10-13.
[3] 潘保良,汪明,王玉万,等.埃普利诺菌素研究进展[J].中国兽医寄生虫病,2003,11(2):59-62
[4] 潘保良,汪明,王玉万,等.埃普利诺菌素注射剂对肉牛血虱的驱杀试验[J].动物医学进展,2003,24(5):119-120.
[5] 蔡进忠,李春花,拉环,等.埃普利诺菌素浇泼剂对牦牛皮蝇幼虫驱除效果试验[J].青海畜牧兽医杂志,2009,39(5):10-12.
[6] Shoop W L,Egerton gerton J R,Eary C H.Eprinomectin:a novel avermectin for use as a topical endectocide for cattle[J].International Journal for Parasitology,1996,26:1237-1242.
[7] Barth D,Hair A,Kunkle B N,et al.Efficacy of eprinomectin against mange mitesin cattle[J].American Journal of Vetrinary Research,1997,58(11):1257-1259.
[8] Pitt S R,Langholff W K,Eagleson J S.The efficacy of eprinomectin against induced infections of immature(fourthlarvalstage) and adult nematode parasites in cattle[J].Veterinary Parasitol,1997,73(1-2):119-128.
[9] Holste J E,Colwell D D,Kumar R.Efficacy of eprinomectin against hypoderma spp in cattle[J].American Journal of Vetrinary Research,1998,59(1):56-58.
[10]Chartier C,Etter E,Pors I.Activity of eprinomectin in goats against experimental infections with Haemontus contortus,Teladorsagia circumcincta and Trichostrongylus colubriformis[J].Veterinary Record,1999,144(4):99-100.
[11]Genchi C,Basano F S,Manfredi.M T,et al.Therapy against gastrointestinal nematodes in cattle:efficacy of eprinomectin[J].Obiettivie Documenti Veterinari,2000,21(5):61-65.
[12]Dorny P,Demeulenaere D,Smets K,et al.Control of gastrointestinal nematodes in first season grazing calves by two strategic treatments with eprinomectin[J].Veterinary Parasitology,2000,89(4):277-286.
[13]Gawor J,Borecka A,Malceewski A.Use of eprinomectin(Eprinex Pour-On)to control natural infection by gastro-intestinal nematodes in goats[J].Medycyna Weterynaryjna,2000,56(6):398-400.
[14]Demiaszkiewicz A W,Malczewski A,LA-chowicz J,et al.Efficacy of Eprinex Pour on [eprinomectin] in the treatment of parasitoses in red deer[J].Magazyn Weterynaryjny,2000,9(46):84-86.
[15] Shoop W,Michael B,Egerton J,et al.Titration of subcutaneously administered eprinomectin against mature and immature nematodes in cattle[J].The Journal of Parasitology,2001,87(6):1466-1469.
[16]Cringoli G,Rinaldi L,Veneziano V,et al.Efficacy of eprinomectin pour-on against gastrointestinal nematode infections in sheep[J].Veterinary Parasitology,2003,112(3):203-209.
[17]Coumendouros K,Tancredi I P,Scott F B,et al.Anthelmintic efficacy of eprinomectin in the control of gastrointestinal nematodes in cattle[J].Revista Brasileira de Parasitologia Veterinaria,2003,12(3):121-124.
[18]Chartier C,Pors I.Duration of activity of topi-cal eprinomectin against experimental infections with Teladorsagia circumcincta and Trichostrongylus colubriformis in goats[J].Veterinary Parasitology,2004,125(3/4):415-419.
[19]Rehbein S,Pitt S R,Rossi L,et al.Efficacy of eprinomectin against Linognathus vituli and Bovicola bovis on calves[J].Veterinary Record,2005,156(4):112-113.
[20] Cringoli G,Rinaldi L,Veneziano V,et al.Effectiveness of eprinomectin pour-on against gastrointestinal nematodes of naturally infected goats[J].Small Ruminant Research,2004,55(1-3):209-213
[21] Cramer L G,Pitt S R,Rehbein S,et al.Persistent efficacy of topical eprinomectin against nematode parasites in cattle[J].Parasitology Research,2000,86(11):944-946
[22] Cringoli G,Rinaldi L,Veneziano V,et al.Efficacy of eprinomectin pour-on against gastrointestinal nematode infections in sheep[J].Veterinary Parasitology,2003,112(3):203-209
[23] Aguirre D H,Gaido A B,Cafrune M M,et al.Eprinomectin pour-on for control of Boophilus microplus (Canestrini) ticks (Acari:Ixodidae) on cattle[J].Veterinary Parasitology,2005,127(2):157-163
[24]Alvinerie M,Sutra J F,Galtier P,et al.Pharmacokinetics of eprinomectin in plasma and milk following topical administration to lactating dairy cattle[J].Research in Veterinary Science,1999,67,(3):229–232.
[25] Bengone D T,Ba M A,Kane Y A.et al.Eprinomectin in dairy zebu Gobra cattle (Bos indicus):plasma kinetics and excretion in milk[J].Parasitology Research,2006,98(6):501-506.
[26] Dupuy J,Sutra J,Alvinerie M,et al.Plasma and milk kinetic of eprinomectin and moxidectin in lactating water buffaloes (Bubalus bubalis) [J].Veterinary Parasitology,2008,157,(3-4):284-290
[27] Anastasio A,Veneziano V,Capurro E,et al.Fate of eprinomectin in goat milk and cheeses with different ripening times following pour-on administration[J].Journal of Food Protection,2005,68(5):1097-1101.
[28] Sutra J F,Chartier C,Galtier P,et al.Determination of eprinomectin in plasma by high-performance liquid chromatography with automated solid phase extraction and fluorescence detection[J].Analyst,1998,123:1525-1527.
[29] Jiang H Y,Hou X L,Ding S Y,et al.Residue Depletion of Eprinomectin in Bovine Tissues after Subcutaneous Administration[J].Journal of Agricultural and Food Chemistry,2005,53 (23):9288–9292.
[30] 江海洋,丁双阳,刘金凤,等.牛皮下注射爱普菌素注射剂后组织残留休药期的建立.畜牧兽医学报,2009,(2):444-450.
[31] Zhang D,Zhang K,Gao J,et al.Anthelmintic efficacy,plasma and milk kinetics of eprinomectin following topical and subcutaneous administration to yaks (Bos grumniens).Exp Parasitol,2015,153:17-21.
[32] Baoliang P,Yuwan W,Zhende P,et al.Pharmacokinetics of eprinomectin in plasma and milk following subcutaneous administration to lactating dairy cattle.Vet Res Commun,2006,30(3):263-270.
[33] Wen H,Pan B,Wang Y,et al.Plasma and milk kinetics of eprinomectin following topical or oral administration to lactating Chinese Holstein cows.Vet Parasitol,2010,174(1-2):72-76.
[34] Bengone-Ndong T,Ba M A,Kane Y,et al.Eprinomectin in dairy zebu Gobra cattle (Bos indicus):plasma kinetics and excretion in milk.Parasitol Res,2006,98(6):501-506.
[35] 潘保良,汪明,王玉万,等.牛奶中埃谱利诺菌素(eprinomectin)荧光高效液相色谱检测方法的建立[J].中国兽医学报,2004,24(2):174-176.
[36]Yu T,Shi Y L,Cai J Z,et al.Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp.following topical administration in yaks.J.vet.Pharmacol.Therap.doi:10.1-6
[37]Committee for Veterinary Medicinal Products(CVMP)-Eprinomectin (Modification),Summary Report,EMEA/MRL/520/98-FINAL[M].The European Agency for the Evaluation of Medicinal Products,1998.
[38]Codex Alimentarius Commission.Maximum Residue Limits for Veterinary Drugs in Foods[M].CAC/MRL,2005.
[39]Code of Federal Regulations Tolerances for Residuesof New Animal Drugs in Food[M].Part 556.227,Title 21,USA,2004.
[2] 殷铭阳,周东辉,刘建枝,等.中国牦牛主要寄生虫病流行现状及防控策略[J].中国畜牧兽医,2014,(5):10-13.
[3] 潘保良,汪明,王玉万,等.埃普利诺菌素研究进展[J].中国兽医寄生虫病,2003,11(2):59-62
[4] 潘保良,汪明,王玉万,等.埃普利诺菌素注射剂对肉牛血虱的驱杀试验[J].动物医学进展,2003,24(5):119-120.
[5] 蔡进忠,李春花,拉环,等.埃普利诺菌素浇泼剂对牦牛皮蝇幼虫驱除效果试验[J].青海畜牧兽医杂志,2009,39(5):10-12.
[6] Shoop W L,Egerton gerton J R,Eary C H.Eprinomectin:a novel avermectin for use as a topical endectocide for cattle[J].International Journal for Parasitology,1996,26:1237-1242.
[7] Barth D,Hair A,Kunkle B N,et al.Efficacy of eprinomectin against mange mitesin cattle[J].American Journal of Vetrinary Research,1997,58(11):1257-1259.
[8] Pitt S R,Langholff W K,Eagleson J S.The efficacy of eprinomectin against induced infections of immature(fourthlarvalstage) and adult nematode parasites in cattle[J].Veterinary Parasitol,1997,73(1-2):119-128.
[9] Holste J E,Colwell D D,Kumar R.Efficacy of eprinomectin against hypoderma spp in cattle[J].American Journal of Vetrinary Research,1998,59(1):56-58.
[10]Chartier C,Etter E,Pors I.Activity of eprinomectin in goats against experimental infections with Haemontus contortus,Teladorsagia circumcincta and Trichostrongylus colubriformis[J].Veterinary Record,1999,144(4):99-100.
[11]Genchi C,Basano F S,Manfredi.M T,et al.Therapy against gastrointestinal nematodes in cattle:efficacy of eprinomectin[J].Obiettivie Documenti Veterinari,2000,21(5):61-65.
[12]Dorny P,Demeulenaere D,Smets K,et al.Control of gastrointestinal nematodes in first season grazing calves by two strategic treatments with eprinomectin[J].Veterinary Parasitology,2000,89(4):277-286.
[13]Gawor J,Borecka A,Malceewski A.Use of eprinomectin(Eprinex Pour-On)to control natural infection by gastro-intestinal nematodes in goats[J].Medycyna Weterynaryjna,2000,56(6):398-400.
[14]Demiaszkiewicz A W,Malczewski A,LA-chowicz J,et al.Efficacy of Eprinex Pour on [eprinomectin] in the treatment of parasitoses in red deer[J].Magazyn Weterynaryjny,2000,9(46):84-86.
[15] Shoop W,Michael B,Egerton J,et al.Titration of subcutaneously administered eprinomectin against mature and immature nematodes in cattle[J].The Journal of Parasitology,2001,87(6):1466-1469.
[16]Cringoli G,Rinaldi L,Veneziano V,et al.Efficacy of eprinomectin pour-on against gastrointestinal nematode infections in sheep[J].Veterinary Parasitology,2003,112(3):203-209.
[17]Coumendouros K,Tancredi I P,Scott F B,et al.Anthelmintic efficacy of eprinomectin in the control of gastrointestinal nematodes in cattle[J].Revista Brasileira de Parasitologia Veterinaria,2003,12(3):121-124.
[18]Chartier C,Pors I.Duration of activity of topi-cal eprinomectin against experimental infections with Teladorsagia circumcincta and Trichostrongylus colubriformis in goats[J].Veterinary Parasitology,2004,125(3/4):415-419.
[19]Rehbein S,Pitt S R,Rossi L,et al.Efficacy of eprinomectin against Linognathus vituli and Bovicola bovis on calves[J].Veterinary Record,2005,156(4):112-113.
[20] Cringoli G,Rinaldi L,Veneziano V,et al.Effectiveness of eprinomectin pour-on against gastrointestinal nematodes of naturally infected goats[J].Small Ruminant Research,2004,55(1-3):209-213
[21] Cramer L G,Pitt S R,Rehbein S,et al.Persistent efficacy of topical eprinomectin against nematode parasites in cattle[J].Parasitology Research,2000,86(11):944-946
[22] Cringoli G,Rinaldi L,Veneziano V,et al.Efficacy of eprinomectin pour-on against gastrointestinal nematode infections in sheep[J].Veterinary Parasitology,2003,112(3):203-209
[23] Aguirre D H,Gaido A B,Cafrune M M,et al.Eprinomectin pour-on for control of Boophilus microplus (Canestrini) ticks (Acari:Ixodidae) on cattle[J].Veterinary Parasitology,2005,127(2):157-163
[24]Alvinerie M,Sutra J F,Galtier P,et al.Pharmacokinetics of eprinomectin in plasma and milk following topical administration to lactating dairy cattle[J].Research in Veterinary Science,1999,67,(3):229–232.
[25] Bengone D T,Ba M A,Kane Y A.et al.Eprinomectin in dairy zebu Gobra cattle (Bos indicus):plasma kinetics and excretion in milk[J].Parasitology Research,2006,98(6):501-506.
[26] Dupuy J,Sutra J,Alvinerie M,et al.Plasma and milk kinetic of eprinomectin and moxidectin in lactating water buffaloes (Bubalus bubalis) [J].Veterinary Parasitology,2008,157,(3-4):284-290
[27] Anastasio A,Veneziano V,Capurro E,et al.Fate of eprinomectin in goat milk and cheeses with different ripening times following pour-on administration[J].Journal of Food Protection,2005,68(5):1097-1101.
[28] Sutra J F,Chartier C,Galtier P,et al.Determination of eprinomectin in plasma by high-performance liquid chromatography with automated solid phase extraction and fluorescence detection[J].Analyst,1998,123:1525-1527.
[29] Jiang H Y,Hou X L,Ding S Y,et al.Residue Depletion of Eprinomectin in Bovine Tissues after Subcutaneous Administration[J].Journal of Agricultural and Food Chemistry,2005,53 (23):9288–9292.
[30] 江海洋,丁双阳,刘金凤,等.牛皮下注射爱普菌素注射剂后组织残留休药期的建立.畜牧兽医学报,2009,(2):444-450.
[31] Zhang D,Zhang K,Gao J,et al.Anthelmintic efficacy,plasma and milk kinetics of eprinomectin following topical and subcutaneous administration to yaks (Bos grumniens).Exp Parasitol,2015,153:17-21.
[32] Baoliang P,Yuwan W,Zhende P,et al.Pharmacokinetics of eprinomectin in plasma and milk following subcutaneous administration to lactating dairy cattle.Vet Res Commun,2006,30(3):263-270.
[33] Wen H,Pan B,Wang Y,et al.Plasma and milk kinetics of eprinomectin following topical or oral administration to lactating Chinese Holstein cows.Vet Parasitol,2010,174(1-2):72-76.
[34] Bengone-Ndong T,Ba M A,Kane Y,et al.Eprinomectin in dairy zebu Gobra cattle (Bos indicus):plasma kinetics and excretion in milk.Parasitol Res,2006,98(6):501-506.
[35] 潘保良,汪明,王玉万,等.牛奶中埃谱利诺菌素(eprinomectin)荧光高效液相色谱检测方法的建立[J].中国兽医学报,2004,24(2):174-176.
[36]Yu T,Shi Y L,Cai J Z,et al.Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp.following topical administration in yaks.J.vet.Pharmacol.Therap.doi:10.1-6
[37]Committee for Veterinary Medicinal Products(CVMP)-Eprinomectin (Modification),Summary Report,EMEA/MRL/520/98-FINAL[M].The European Agency for the Evaluation of Medicinal Products,1998.
[38]Codex Alimentarius Commission.Maximum Residue Limits for Veterinary Drugs in Foods[M].CAC/MRL,2005.
[39]Code of Federal Regulations Tolerances for Residuesof New Animal Drugs in Food[M].Part 556.227,Title 21,USA,2004.