Pharmaco-parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle
Corresponding Author
C. Canton
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Correspondence
Candela Canton, Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina.
Email: [email protected]
Search for more papers by this authorL. Ceballos
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorM. P. Domínguez
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorL. Moreno
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Fiel
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorG. Bernat
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Farías
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Lanusse
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorL. Alvarez
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorCorresponding Author
C. Canton
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Correspondence
Candela Canton, Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina.
Email: [email protected]
Search for more papers by this authorL. Ceballos
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorM. P. Domínguez
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorL. Moreno
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Fiel
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorG. Bernat
Laboratorio de Parasitología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Farías
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorC. Lanusse
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorL. Alvarez
Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Tandil, Argentina
Search for more papers by this authorAbstract
The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and co-administered to calves naturally infected with susceptible gastrointestinal nematodes. The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control. RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance.
REFERENCES
- Alvarez, L., Lifschitz, A., Entrocasso, C., Manazza, J., Mottier, L., Borda, B., … Lanusse, C. (2008). Evaluation of the interaction between ivermectin and albendazole following their combined use in lambs. Journal of Veterinary Pharmacology and Therapeutics, 31, 230–239.
- Alvarez, L., Sanchez, S., & Lanusse, C. (1999). In vivo and ex vivo uptake of albendazole and its sulphoxide metabolite by cestode parasites: Relationship with their kinetic behaviour in sheep. Journal of Veterinary Pharmacology and Therapeutics, 22, 77–86.
- Anderson, N., Martin, P. J., & Jarret, R. G. (1988). Mixtures of anthelmintics: A strategy against resistance. Australian Veterinary Journal, 65, 62–64.
- Anderson, N., Martin, P. J., & Jarret, R. G. (1991). The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole. Australian Veterinary Journal, 68, 127–132.
- Bartram, D. J., Leathwick, D. M., Taylor, M. A., Geurden, T., & Maeder, S. J. (2012). The role of combination anthelmintic formulations in the sustainable control of sheep nematodes. Veterinary Parasitology, 186, 151–158.
- Campbell, W. (1990). Benzimidazoles: Veterinary uses. Parasitology Today, 6, 130–133.
- Canton, C., Ceballos, L., Fiel, C., Moreno, L., Domingo Yagüez, P., Bernat, G., … Alvarez, L. (2017). Resistant nematodes in cattle: Pharmaco-therapeutic assessment of the ivermectin- ricobendazole combination. Veterinary Parasitology, 234, 40–48.
10.1016/j.vetpar.2016.12.021 Google Scholar
- Charlier, J., De Waele, V., Ducheyne, E., van der Voort, M., Vande Velde, F., & Claerebout, E. (2015). Decision making on helminths in cattle: Diagnostics, economics and human behaviour. Irish Veterinary Journal, 69, 1–5.
- Coles, G. C., Bauer, C., Borgsteede, F. H. M., Geerts, S., Klei, T. R., & Taylor, M. A. (1992). World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance. Veterinary Parasitology, 44, 35–44.
- Courtney, C. H., & Roberson, E. (1995). Antinematodal drugs. In R. Adams (Ed.), Veterinary pharmacology and therapeutics. Iowa, USA: Iowa State University Press.
- Cromie, L., Ferry, M., Couper, A., Fields, C., & Taylor, S. M. (2006). Pharmacokinetics of a novel closantel/ivermectin injection in cattle. Journal of Veterinary Pharmacology and Therapeutics, 29, 205–211.
- Dobson, R. J., Besier, R. B., Barnes, E. H., Love, S. C., Vizard, A., Bell, K., & Le Jambre, L. F. (2001). Principles for the use of macrocyclic lactones to minimise selection for resistance. Australian Veterinary Journal, 79, 756–761.
- Dobson, R. J., Hosking, B. C., Besier, R. B., Love, S., Larsen, J. W. A., Rolfe, P. F., & Bailey, J. N. (2011). Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems. Australian Veterinary Journal, 89, 160–166.
- Dobson, R. J., Lejambre, L., & Gill, J. H. (1996). Management of anthelmintic resistance: Inheritance of resistance and selection with persistent drugs. International Journal for Parasitology, 26, 993–1000.
- Dorn, H., & Federmann, M. (1976). Citarin-L Spot-on- A new form of administration of an established anthelmintic [levamisole]. Veterinary Medical Review, 1, 5–17.
- Entrocasso, C., Alvarez, L., Manazza, J., Lifschitz, A., Borda, B., Virkel, G., … Lanusse, C. (2008). Clinical efficacy assessment of the albendazole–ivermectin combination in lambs parasitized with resistant nematodes. Veterinary Parasitology, 155, 249–256.
- Fernández, A., Fiel, C., & Steffan, P. (1999). Study on the inductive factors of hypobiosis of Ostertagia ostertagi in cattle. Veterinary Parasitology, 81, 295–307.
10.1016/S0304-4017(98)00252-0 Google Scholar
- Fiel, C., Cristel, S., Anziani, O., Descarga, C., Cetrá, B., Romero, J., … Steffan, P. (2015). A survey on anthelmintic resistance in grazing cattle of Argentina. In Proceedings of the 25th. International Conference of the World Association for the Advancement of Veterinary Parasitology (pp. 424). Liverpool, UK.
- Geary, T. G., Hosking, B. C., Skuce, P. J., von Samson-Himmelstjerna, G., Maeder, S., Holdsworth, P., … Vercruysse, J. (2012). World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) Guideline: Anthelmintic combination products targeting nematode infections of ruminants and horses. Veterinary Parasitology, 190, 306–316.
- Gibaldi, M., & Perrier, D. (1982). Pharmacokinetics, 2nd ed. Revised and Expanded. New York, USA: Marcel Dekker.
- Hart, J. A., James, P. S., & Curr, C. (1969). The anthelmintic efficiency of laevo-tetramisole hydrochloride against nematode parasites of sheep and cattle. Australian Veterinary Journal, 45, 73–77.
- Kaplan, R. M., & Vidyashankar, A. N. (2012). An inconvenient truth: Global worming and anthelmintic resistance. Veterinary Parasitology, 186, 70–78.
- Lacey, E. (1990). Mode of action of benzimidazoles. Parasitology Today, 6, 112–115.
- Lanusse, C., Alvarez, L., & Lifschitz, A. (2014). Pharmacological knowledge and sustainable anthelmintic therapy in ruminants. Veterinary Parasitology, 204, 18–33.
- Lanusse, C., Lifschitz, A., & Alvarez, L. (2015). Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan. Veterinary Parasitology, 212, 35–46.
- Lanusse, C., Virkel, G., Sanchez, S., Alvarez, L., Lifschitz, A., Imperiale, F., & Monfrinotti, A. (1998). Ricobendazole kinetics and availability following subcutaneous administration of a novel injectable formulation to calves. Research in Veterinary Science, 65, 5–10.
- Leathwick, D. M. (2012). Modelling the benefits of a new class of anthelmintic in combination. Veterinary Parasitology, 186, 93–100.
- Leathwick, D. M., Miller, C. M., Sauermann, C. S., Candy, P. M., Ganesh, S., Fraser, K., & Waghorn, T. S. (2016). The efficacy and plasma profiles of abamectin plus levamisole combination anthelmintics administered as oral and pour-on formulations to cattle. Veterinary Parasitology, 227, 85–92.
10.1016/j.vetpar.2016.07.031 Google Scholar
- Leathwick, D. M., Waghorn, T. S., Miller, C. M., Candy, P. M., & Oliver, A. B. (2012). Managing anthelmintic resistance – Use of a combination anthelmintic and leaving some lambs untreated to slow the development of resistance to ivermectin. Veterinary Parasitology, 187, 285–294.
- MAFF (Ministry of Agriculture, Fisheries and Food) (1986). Manual of veterinary parasitological laboratory techniques. London: Her Majesty's Stationery Office.
- Mason, P. C., & McKay, C. H. (2006). Field studies investigating anthelmintic resistance in young cattle on five farms in New Zealand. New Zealand Veterinary Journal, 54, 318–322.
- McKenna, P. (1990a). The detection of anthelmintic resistance by the faecal egg count reduction test: An examination of some of the factors affecting performance and interpretation. New Zealand Veterinary Journal, 38, 142–147.
- Mckenna, P. B. (1990b). The use of benzimidazole-levamisole mixtures for the control and prevention of anthelmintic resistance in sheep nematodes: An assessment of their likely effects. New Zealand Veterinary Journal, 38, 45–49.
- Perrier, D., & Mayersohn, M. (1982). Non-compartmental determination of the steady-state volume of distribution for any mode of administration. Journal of Pharmaceutical Science, 71, 372–373.
- Prescott, J. F. (2000). Antimicrobial drug action and interaction: An introduction. In J. F. Prescott, J. D. Baggot, & R. D. Walker (Eds.), Antimicrobial Therapy in Veterinary Medicine (pp. 3–11). Iowa: Iowa State Press.
- Prichard, R. K. (2002). Resistance against macrocyclic lactones. In J. Vercruysse, & R. S. Rew (Eds.), Macrocyclic lactones antiparasitic therapy (pp. 163–182). Wallingford, UK: CABI Publishing.
- Roberts, F., & O'sullivan, P. (1950). Methods for egg counts and larval cultures for strongyles infesting the gastrointestinal tract of cattle. Crop Pasture Science, 1, 99–102.
- Robertson, S., & Martin, R. (1993). Levamisole-activated single-channel currents from muscle of the nematode parasite Ascaris suum. British Journal of Pharmacology, 108, 170–178.
- Smith, L. L. (2014). Combination anthelmintics effectively control ML-resistant parasites; a real-world case history. Veterinary Parasitology, 204, 12–17.
- Steffan, P. E., Fiel, C. A., Ferreyra, D. A., & Monfrinotti, A. (2002). Eficacia del ricobendazole –vía subcutánea- contra los nematodes gastrointestinales del bovino. Revista de Investigación Agropecuarias, 31, 89–101.
- Suarez, G., Alvarez, L., Castells, D., Moreno, L., Fagiolino, P., & Lanusse, C. (2014). Evaluation of pharmacological interactions after administration of a levamisole, albendazole and ivermectin triple combination in lambs. Veterinary Parasitology, 201, 110–119.
10.1016/j.vetpar.2013.12.015 Google Scholar
- Williams, J. C. (1991). Efficacy of albendazole, levamisole and fenbendazole against gastrointestinal nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae. Veterinary Parasitology, 40, 59–71.
- Williams, J. C., Knox, J. W., Marbury, K. S., Swalley, R. A., & Eddi, C. S. (1991). Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January). Veterinary Parasitology, 40, 73–85.
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