Efficacy of Novel Formulations of Ivermectin and Albendazole in Parasitic Infections of Sheep in the Altai Mountains of Russia
-
Victor Alexeevich Marchenko
,
Salavat Samadovich Khalikov
,
Elena Alexandrovna Efremova
,
Mikhail Mikhaylovich Ilyin (Ju)
Abstract
Background: Parasitic infections are widespread in sheep farms of the Russian Federation, including Siberia. The infection of sheep with helminths and parasitic arthropods with a range of 70% to 100% in different regions, contributes to a decrease in the productivity and quality of products, and even death of animals. This study aimed to formulate drugs with pronounced parasiticidal effects based on ivermectin and albendazole, widely used to treat animal entomoses and helminth infections.
Methods: New formulations in the form of solid dispersed compositions were prepared by mechanochemical modification of ivermectin and albendazole using arabinogalactan polysaccharide. The efficacy of preparations on gastrointestinal strongylosis and monieziosis, and melophagosis of sheep was determined by parasitological examination and analysis of feces and urine.
Results: The new formulations demonstrated increased solubility and parasiticidal activity due to the formation of inclusion complexes when interact with water. The maximum efficacy values (> 95% efficiency) against intestinal Strongylida and Moniezia expansa, and ectoparasitic Melophagus ovinus were seen in doses lower than the recommended doses of the starting drugs.
Conclusion: The increased parasiticidal activity of innovative compositions can be explained by increased water solubility and bioavailability of the preparations, due to formation of inclusion complexes. The results of this study suggests the possibility of a significant reduction in the dosages of composed substances without losing their parasiticidal activity.
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2. Puzanova EV. Forecast of epizootic situation in main helminthosis of farm livestock in the Russian Federation for 2019. Rus J Parasitol. 2019;2:28-35.
3. Marchenko VA, Efremova EA. Theory and practice of control of parasitic diseases. Moscow: All-Russia Skyrabin Society of Helminthologists Division of Biological Sciences of the Russian Academy of Sciences; 2019.
4. Efremova EA, Marchenko VA. Features of the structure of the helminth complex and the dynamics of sheep infection in the Altai Republic. Siberian Bull Agri Sci. 2014;6:82-9.
5. Marchenko VA, Zemirov YS. Entomoses of sheep of the Altai Mountains. Novosibirsk Agricultural Library of the Siberian Department, 2012.
6. Marchenko VA. Theory and practice of control of parasitic diseases: Moscow: Publishing House Science; 2019.
7. Marchenko VA, Efremova EA, Makaseev VK. Unified system of medical and preventive measures for sheep zooparasitosis in the Altai Republic. Novosibirsk: Gorno-Altaysk University, 2013.
8. Chebyshev NV, Epiphany YK, Grishina EA. Helminthosis: Organ-systemic processes in their pathogenesis and treatment: Medicina; 1998.
9. Campbell WC. Benzimidazoles: veterinary uses. Parasitol Today. 1990;6(4):130-3.
10. Himonas CA, Liakos V. Efficacy of albendazole against Dicrocoelium dendriticum in sheep. Vet Rec. 1980;107(12):288-9.
11. Arkhipov IA. Anthelminthics: Pharmacology and application. Moscow: Russian Academy of Agricultural Sciences; 2009.
12. Bradley RE, Randell WF, Armstrong DA. Anthelmintic efficacy of albendazole in calves with naturally acquired Fasciola hepatica infections. Am J Vet Res. 1981;42(6):1062-4.
13. Campbell WC. Ivermectin: an update. Parasitol Today. 1985;1(1):10-6.
14. Campbell WC, Benz GW. Ivermectin: a review of efficacy and safety. J Vet Pharmacol Ther. 1984;7(1):1-16.
15. Hanif MA, Mostofa M, Choudhury ME. Efficacy of ivermectin (pour on formulation) against ectoparasites in sheep. Bangl J Vet Med. 2005;3(2):140-3.
16. Sisodia S, Pathak K, Kapoor M. Anthelmintic efficacy of doramectin and ivermectin against naturally occurring ectoparasites and gastrointestinal nematodes of sheep. Indian Vet J. 1996;73:1167-71.
17. Belova EE, Smirnov AA, Sadov KM. Efficiency of praziver helminthiasis of horses. Rus J Parasitol. 2010;13(4):28-35.
18. Entrocasso C, Alvarez L, Manazza J, et al. Clinical efficacy assessment of the albendazole-ivermectin combination in lambs parasitized with resistant nematodes. Vet Parasitol. 2008;155(3-4):249-56.
19. Kalaiselvan R, Mohanta GP, Madhusudan S, et al. Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques. Pharmazie. 2007;62(8):604-7.
20. Ullio Gamboa GV, Pensel PE, Elissondo MC, et al. Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus. Exp Parasitol. 2019;198:79-86.
21. Sun Y, Chen D, Pan Y, et al. Nanoparticles for antiparasitic drug delivery. Drug Deliv. 2019;26(1):1206-21.
22. Arkhipov IA, Khalikov SS, Dushkin AV. Supramolecular complexes of anthelmintic benzimidazole preparations, preparation and properties. New Authors; Moscow, 2017.
23. Dushkin AV, Suntsova LP, Khalikov SS. Mechanochemical technology to increase the solubility of drugs. Fund Res. 2013;2(1):448-55.
24. Khalikov SS, Dushkin AV, Khalikov MS. Mechanochemical modification of the properties of anthelmintic drugs. Chem Sus Dev. 2011;19(6):705-10.
25. Lagereva E, Abramov V, Musaev M, et al. Efficacy of supramolecular complex based on albendazole and triclabendazole against fasciolosis and gastro-intestinal nematodosis of sheep. Rus J Parasitol. 2019;13(2):82-8.
26. Varlamova AI, Dolgoshev VA, Sadov KM. Efficiency of supramolecular complexes of anthelmintics in gastrointestinal sheep strong intestinal infections. Rus J Parasitol. 2015(1):71-4.
27. Anipov KA, Pominova TY, Pereverzeva EI, et al. Preparation and physicochemical properties of polymeric complexes of methyl benzimidazol-2-ylcarbamate with apple pectin. Chem Nat Comp. 1995;31:753-6.
28. Burkhanova ND, Yugai SM, Khalikov SS, et al. Interaction of drugs with microcrystalline cellulose at the molecular and supermolecular levels. Chem Nat Comp. 1997;33:340-6.
29. Parmar KR, Patel KA, Shah SR, et al. Inclusion complexes of lamotrigine and hydroxy propyl β-cyclodextrin: solid state characterization and dissolution studies. J Incl Phenom Macrocycl Chem. 2009;65(3):263-268.
30. Chistyachenko YS, Meteleva ES, Pakharukova MY, et al. A physicochemical and pharmacological study of the newly synthesized complex of albendazole and the polysaccharide arabinogalactan from larch wood. Curr Drug Deliv. 2015;12(5):477-90.
31. Khabriev RU. Guidelines for the experimental (preclinical) study of new pharmacological substances. Moscow: Publishing House Medicine; 2005.
32. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. Strasbourg, 1986.
33. The order of the Ministry of Health of the Russian Federation, 2016 April 1st, No. 200 “On the approval of the rules of good clinical practice. Moscow, 2016.
34. Kalashnikov AP, Fisin VF, Shcheglova VV. Norms and diets of livestock feeding, Ag-ricultural Academy, Moscow (2003).
35. Manual of Veterinary Parasitological Laboratory Techniques. In: MAFF (Ministry of Agriculture FaF, ditor. ADAS, HMSO, UK, 1986.
36. Wood IB, Amaral NK, Bairden K, et al. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine). Vet Parasitol. 1995;58(3):181-213.
37. Kondrakhin IP, Arkhipov AV, Levchenko VI. Methods of veterinary clinical laboratory diagnostics. Moscow: Kolos; 2004.
38. Pandit S, Ghosh JD, Chinya A, et al. Evaluation of anthelmintic efficacy of ivermectin, levamisole and albendazole against naturally occurring gastrointestinal nematodosis in Garole sheep. J Vet Parasitol. 2009;23:121-5.
39. Vercruysse J. Macrocyclic Lactones in Antiparasitic Therapy. USA CABI Publishing; 2002.
40. Kalia A, Poddar M. Solid dispersions: An approach towards enhancing dissolution rate. Int J Pharm Pharm Sci. 2011;3(4):9-19.
41. Wagh VT, Wagh RD. Solid dispersion techniques for enhancement of solubilization and bioavailability of poorly water soluble Drugs- A review. Int J Pharm Tech. 2015;6(4):3027-45.
42. Yadav B, Tanwar YS. Applications of solid dispersions. J Chem Pharm Res. 2015;7(2):965-78.
43. Castro SG, Bruni SS, Lanusse CE, et al. Improved albendazole dissolution rate in pluronic 188 solid dispersions. AAPS PharmSciTech. 2010;11(4):1518-25.
44. Alvarez L, Lifschitz A, Entrocasso C, et al. Evaluation of the interaction between ivermectin and albendazole following their combined use in lambs. J Vet Pharmacol Ther. 2008;31(3):230-9.
45. Canton C, Canton L, Domínguez MP, et al. Field trial assessment of ivermectin pharmacokinetics and efficacy against susceptible and resistant nematode populations in cattle. Vet Parasitol. 2018;256:43-9.
46. Kalinnikova TB, Gainutdinov MK, Shagidullin RR. Resistance to anthelmintic drugs: a problem and solutions. Veterinarian. 2018;5:36-41.
47. Varlamova AI, Arkhipov IA, Odoevskaya IM. The effectiveness of the dosage form of fenbendazole, obtained on the basis of nanotechnology and targeted delivery of the Drug Delivery System for helminthiases. Med Parasitol Parasit Dis. 2014(4):43-4.
48. Arkhipov IA, Khalikov SS, Sadov KM, et al. Influence of mechanochemical technology on anthelmintic efficacy of the supramolecular complex of fenbendazole with polyvinylpyrrolidone. J Adv Vet Anim Res. 2019;6(1):133-41.
2. Puzanova EV. Forecast of epizootic situation in main helminthosis of farm livestock in the Russian Federation for 2019. Rus J Parasitol. 2019;2:28-35.
3. Marchenko VA, Efremova EA. Theory and practice of control of parasitic diseases. Moscow: All-Russia Skyrabin Society of Helminthologists Division of Biological Sciences of the Russian Academy of Sciences; 2019.
4. Efremova EA, Marchenko VA. Features of the structure of the helminth complex and the dynamics of sheep infection in the Altai Republic. Siberian Bull Agri Sci. 2014;6:82-9.
5. Marchenko VA, Zemirov YS. Entomoses of sheep of the Altai Mountains. Novosibirsk Agricultural Library of the Siberian Department, 2012.
6. Marchenko VA. Theory and practice of control of parasitic diseases: Moscow: Publishing House Science; 2019.
7. Marchenko VA, Efremova EA, Makaseev VK. Unified system of medical and preventive measures for sheep zooparasitosis in the Altai Republic. Novosibirsk: Gorno-Altaysk University, 2013.
8. Chebyshev NV, Epiphany YK, Grishina EA. Helminthosis: Organ-systemic processes in their pathogenesis and treatment: Medicina; 1998.
9. Campbell WC. Benzimidazoles: veterinary uses. Parasitol Today. 1990;6(4):130-3.
10. Himonas CA, Liakos V. Efficacy of albendazole against Dicrocoelium dendriticum in sheep. Vet Rec. 1980;107(12):288-9.
11. Arkhipov IA. Anthelminthics: Pharmacology and application. Moscow: Russian Academy of Agricultural Sciences; 2009.
12. Bradley RE, Randell WF, Armstrong DA. Anthelmintic efficacy of albendazole in calves with naturally acquired Fasciola hepatica infections. Am J Vet Res. 1981;42(6):1062-4.
13. Campbell WC. Ivermectin: an update. Parasitol Today. 1985;1(1):10-6.
14. Campbell WC, Benz GW. Ivermectin: a review of efficacy and safety. J Vet Pharmacol Ther. 1984;7(1):1-16.
15. Hanif MA, Mostofa M, Choudhury ME. Efficacy of ivermectin (pour on formulation) against ectoparasites in sheep. Bangl J Vet Med. 2005;3(2):140-3.
16. Sisodia S, Pathak K, Kapoor M. Anthelmintic efficacy of doramectin and ivermectin against naturally occurring ectoparasites and gastrointestinal nematodes of sheep. Indian Vet J. 1996;73:1167-71.
17. Belova EE, Smirnov AA, Sadov KM. Efficiency of praziver helminthiasis of horses. Rus J Parasitol. 2010;13(4):28-35.
18. Entrocasso C, Alvarez L, Manazza J, et al. Clinical efficacy assessment of the albendazole-ivermectin combination in lambs parasitized with resistant nematodes. Vet Parasitol. 2008;155(3-4):249-56.
19. Kalaiselvan R, Mohanta GP, Madhusudan S, et al. Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques. Pharmazie. 2007;62(8):604-7.
20. Ullio Gamboa GV, Pensel PE, Elissondo MC, et al. Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus. Exp Parasitol. 2019;198:79-86.
21. Sun Y, Chen D, Pan Y, et al. Nanoparticles for antiparasitic drug delivery. Drug Deliv. 2019;26(1):1206-21.
22. Arkhipov IA, Khalikov SS, Dushkin AV. Supramolecular complexes of anthelmintic benzimidazole preparations, preparation and properties. New Authors; Moscow, 2017.
23. Dushkin AV, Suntsova LP, Khalikov SS. Mechanochemical technology to increase the solubility of drugs. Fund Res. 2013;2(1):448-55.
24. Khalikov SS, Dushkin AV, Khalikov MS. Mechanochemical modification of the properties of anthelmintic drugs. Chem Sus Dev. 2011;19(6):705-10.
25. Lagereva E, Abramov V, Musaev M, et al. Efficacy of supramolecular complex based on albendazole and triclabendazole against fasciolosis and gastro-intestinal nematodosis of sheep. Rus J Parasitol. 2019;13(2):82-8.
26. Varlamova AI, Dolgoshev VA, Sadov KM. Efficiency of supramolecular complexes of anthelmintics in gastrointestinal sheep strong intestinal infections. Rus J Parasitol. 2015(1):71-4.
27. Anipov KA, Pominova TY, Pereverzeva EI, et al. Preparation and physicochemical properties of polymeric complexes of methyl benzimidazol-2-ylcarbamate with apple pectin. Chem Nat Comp. 1995;31:753-6.
28. Burkhanova ND, Yugai SM, Khalikov SS, et al. Interaction of drugs with microcrystalline cellulose at the molecular and supermolecular levels. Chem Nat Comp. 1997;33:340-6.
29. Parmar KR, Patel KA, Shah SR, et al. Inclusion complexes of lamotrigine and hydroxy propyl β-cyclodextrin: solid state characterization and dissolution studies. J Incl Phenom Macrocycl Chem. 2009;65(3):263-268.
30. Chistyachenko YS, Meteleva ES, Pakharukova MY, et al. A physicochemical and pharmacological study of the newly synthesized complex of albendazole and the polysaccharide arabinogalactan from larch wood. Curr Drug Deliv. 2015;12(5):477-90.
31. Khabriev RU. Guidelines for the experimental (preclinical) study of new pharmacological substances. Moscow: Publishing House Medicine; 2005.
32. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. Strasbourg, 1986.
33. The order of the Ministry of Health of the Russian Federation, 2016 April 1st, No. 200 “On the approval of the rules of good clinical practice. Moscow, 2016.
34. Kalashnikov AP, Fisin VF, Shcheglova VV. Norms and diets of livestock feeding, Ag-ricultural Academy, Moscow (2003).
35. Manual of Veterinary Parasitological Laboratory Techniques. In: MAFF (Ministry of Agriculture FaF, ditor. ADAS, HMSO, UK, 1986.
36. Wood IB, Amaral NK, Bairden K, et al. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine). Vet Parasitol. 1995;58(3):181-213.
37. Kondrakhin IP, Arkhipov AV, Levchenko VI. Methods of veterinary clinical laboratory diagnostics. Moscow: Kolos; 2004.
38. Pandit S, Ghosh JD, Chinya A, et al. Evaluation of anthelmintic efficacy of ivermectin, levamisole and albendazole against naturally occurring gastrointestinal nematodosis in Garole sheep. J Vet Parasitol. 2009;23:121-5.
39. Vercruysse J. Macrocyclic Lactones in Antiparasitic Therapy. USA CABI Publishing; 2002.
40. Kalia A, Poddar M. Solid dispersions: An approach towards enhancing dissolution rate. Int J Pharm Pharm Sci. 2011;3(4):9-19.
41. Wagh VT, Wagh RD. Solid dispersion techniques for enhancement of solubilization and bioavailability of poorly water soluble Drugs- A review. Int J Pharm Tech. 2015;6(4):3027-45.
42. Yadav B, Tanwar YS. Applications of solid dispersions. J Chem Pharm Res. 2015;7(2):965-78.
43. Castro SG, Bruni SS, Lanusse CE, et al. Improved albendazole dissolution rate in pluronic 188 solid dispersions. AAPS PharmSciTech. 2010;11(4):1518-25.
44. Alvarez L, Lifschitz A, Entrocasso C, et al. Evaluation of the interaction between ivermectin and albendazole following their combined use in lambs. J Vet Pharmacol Ther. 2008;31(3):230-9.
45. Canton C, Canton L, Domínguez MP, et al. Field trial assessment of ivermectin pharmacokinetics and efficacy against susceptible and resistant nematode populations in cattle. Vet Parasitol. 2018;256:43-9.
46. Kalinnikova TB, Gainutdinov MK, Shagidullin RR. Resistance to anthelmintic drugs: a problem and solutions. Veterinarian. 2018;5:36-41.
47. Varlamova AI, Arkhipov IA, Odoevskaya IM. The effectiveness of the dosage form of fenbendazole, obtained on the basis of nanotechnology and targeted delivery of the Drug Delivery System for helminthiases. Med Parasitol Parasit Dis. 2014(4):43-4.
48. Arkhipov IA, Khalikov SS, Sadov KM, et al. Influence of mechanochemical technology on anthelmintic efficacy of the supramolecular complex of fenbendazole with polyvinylpyrrolidone. J Adv Vet Anim Res. 2019;6(1):133-41.
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| Issue | Vol 16 No 2 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v16i2.6268 | |
| Keywords | ||
| Albendazole Arabinogalactan Efficacy Ivermectin Parasiticide | ||
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How to Cite
1.
Alexeevich Marchenko V, Samadovich Khalikov S, Alexandrovna Efremova E, Mikhaylovich Ilyin (Ju) M. Efficacy of Novel Formulations of Ivermectin and Albendazole in Parasitic Infections of Sheep in the Altai Mountains of Russia. Iran J Parasitol. 2021;16(2):199-208.
