The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

Particle and Fibre Toxicology

Klemens J Krieger¹  Wolfgang Jiritschka¹  Andrew Leisewitz²  Andreas Turberg¹  Eva M Kruedewagen¹  Eva Schoenhense³  Ulrich Ebbinghaus-Kintscher³  Dorothee Stanneck¹ 

[1] Bayer Animal Health GmbH, D-51368 Leverkusen, Germany;Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Department of Companion Animal Clinical Studies, Private Bag X04, Onderstepoort, Pretoria 0110, South Africa;Bayer CropScience AG, D-51368 Leverkusen, Germany

关键词: Slow release;    Efficacy;    Synergism;    Dog;    Cat;    Collar;    Flumethrin;    Imidacloprid;   

Others  :  1232499
DOI  :  10.1186/1756-3305-5-73

 received in 2012-01-17, accepted in 2012-04-12,  发布年份 2012

【 摘 要 】

Background

The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies.

Methods

The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.

Results

An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.

Conclusion

Here we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.

【 授权许可】

   
2012 Stanneck et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

【 参考文献 】

• [1]Chomel B: Tick-borne infections in dogs-an emerging infectious threat. Vet Parasitol 2011, 179(4):294-301.
• [2]Ferroglio E, Poggi M, Trisciuoglio A: Evaluation of 65% permethrin spot-on and deltamethrin-impregnated collars for canine Leishmania infantum infection prevention. Zoonoses Public Hlth 2008, 55(3):145-148.
• [3]Maroli MMM, Khoury CKC: Prevention and control of leishmaniasis vectors: current approaches. Parassitologia (Rome) 2004, 46(1-2):211-215.
• [4]Reithinger R, Coleman PG, Alexander B, Vieira EP, Assis G, Davies CR: Are insecticide-impregnated dog collars a feasible alternative to dog culling as a strategy for controlling canine visceral leishmaniasis in Brazil? Int J Parasitol 2004, 34(1):55-62.
• [5]Reithinger R, Ceballos L, Stariolo R, Davies CR, Gurtler RE: Chagas disease control: deltamethrin-treated collars reduce Triatoma infestans feeding success on dogs. T Roy Soc Trop Med H 2005, 99(7):502-508.
• [6]Shaw SE, Day MJ, Birtles RJ, Breitschwerdt EB: Tick-borne infectious diseases of dogs. Trends Parasitol 2001, 17(2):74-80.
• [7]Dryden MW, Payne PA: Biology and control of ticks infesting dogs and cats in North America. Vet Ther 2004, 5(2):139-154.
• [8]Cummings J, Vickers L, Marbaugh J: Evaluation of veterinary dispensing records to measure "clinic compliance" with recommended heartworm prevention programs. Proceedings of the Heartworm Prevention Programs '95 1995: American Heartworm Society 1995, 183-186.
• [9]Rohrbach BW, Lutzy A, Patton S: Attributes, knowledge, beliefs, and behaviors relating to prevention of heartworm in dogs among members of a national hunting dog club. Vet Parasitol 2011, 176(4):324-332.
• [10]Rohrbach BW, Odoi A, Patton S: Survey of heartworm prevention practices among members of a national hunting dog club. J Am Anim Hosp Assoc 2011, 47(3):161-169.
• [11]Van Vlaenderen I, Nautrup BP, Gasper SM: Estimation of the clinical and economic consequences of non-compliance with antimicrobial treatment of canine skin infections. Prev Vet Med 2011, 99(2-4):201-210.
• [12]Grieve GA, Neuhoff KT, Thomas RM, Welborn LV, Albers JW, Parone JC: Practice tips for improving compliance: The Path to Higher Care. Denver (CO): American Animal Hospital Association; 2003.
• [13]Gates MC, Nolan TJ: Factors influencing heartworm, flea, and tick preventative use in patients presenting to a veterinary teaching hospital. Prev Vet Med 2010, 93(2-3):193-200.
• [14]Zajac AM, Sangster NC, Geary TG: Why veterinarians should care more about parasitology. Parasitol Today 2000, 16(12):504-506.
• [15]Elfassy OJ, Goodman FW, Levy SA, Carter LL: Efficacy of an amitraz-impregnated collar in preventing transmission of Borrelia burgdorferi by adult Ixodes scapularis to dogs. J Am Vet Med Assoc 2001, 219(2):185-189.
• [16]Estrada-Pena A, Reme C: Efficacy of a collar impregnated with amitraz and pyriproxyfen for prevention of experimental tick infestations by Rhipicephalus sanguineus, Ixodes ricinus, and Ixodes scapularis in dogs. J Am Vet Med Assoc 2005, 226(2):221-224.
• [17]van den Bos RH, Curtis RJ: The use of a 4% (w/w) deltamethrin collar (Scalibor ProtectorBand) in the extended control of ticks on dogs. Ex Appl Acarol 2002, 28(1-4):297-303.
• [18]Fourie LJ, Stanneck D, Horak IG: The efficacy of collars impregnated with flumethrin and propoxur against experimental infestations of adult Rhipicephalus sanguineus on dogs. J S Afr Vet Assoc 2003, 74(4):123-126.
• [19]Zlotkin E: The insect voltage-gated sodium channel as target of insecticides. Annu Rev Res Biol 1999, 44:429-455.
• [20]de Weille JR, Leinders T: The action of pyrethroids on sodium channels in myelinated nerve fibres and spinal ganglion cells of the frog. Brain Res 1989, 482(2):324-332.
• [21]Mencke N, Jeschke P: Therapy and prevention of parasitic insects in veterinary medicine using imidacloprid. Curr Tops Medl Chem 2002, 2(7):701-715.
• [22]Yamamoto I, Yabuta G, Tomizawa M, Saito T, Miyamoto T, Kagabu S: Molecular mechanism for selective toxicity of niotinoids and neonicotinoids. J Pest Sci 1995, 20:33-40.
• [23]Yamamoto I, Tomizawa M, Saito T, Miyamoto T, Walcott DE, Sumikawa K: Structural factors contributing to insecticidal and selective actions of neonicotinoids. Arch Insect Biochem Physiol 1998, 37:24-32.
• [24]Hellmann K, Knoppe T, Krieger K, Stanneck D: European multicenter field trial on the efficacy and safety of a topical formulation of imidacloprid and permethrin (Advantix) in dogs naturally infested with ticks and/or fleas. Parasitol Res 2003, 90(Suppl 3):S125-S126.
• [25]S D, Kruedewagen EM, Fourie JJ, Horak IG, Davis WL, Krieger KJ: The efficacy of an imidacloprid/flumethrin collar against fleas and ticks on cats. Parasite Vector 2012. Under review
• [26]Stanneck D, Kruedewagen EM, Fourie JJ, Horak IG, Davis WL, Krieger KJ: The efficacy of an imidacloprid/flumethrin collar against fleas, ticks, mites and lice on dogs. Parasite Vector 2012. Under review
• [27]Stanneck D, Rass J, Radeloff I, Le Sueur C, Hellmann K, Krieger K: Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe. Parasite Vector 2012. Under review
• [28]Prugh J, Della Croce K, Levine RB: Effects of the steroid hormone, 20-hydroxyecdysone, on the growth of neurites by identified insect motoneurons in vitro. Dev Biol 1992, 154(2):331-347.
• [29]Oland LA, Muller T, Kettenmann H, Hayashi J: Preparation of primary cultures and acute slices of the nervous system of the moth Manduca sexta. J Neurosci Meth 1996, 69(1):103-112.
• [30]Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ: Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 1981, 391(2):85-100.
• [31]Fenwick EM, Marty A, Neher E: A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol (Lond) 1982, 331:577-597.
• [32]Guideline for the testing and evaluation of the efficacy of antiparasitic substances for the treatment and prevention of tick and flea infestation in dogs and cats [http:/ / www.ema.europa.eu/ docs/ en_GB/ document_library/ Scientific_guideline/ 2009/ 10/ WC 500004639.pdf] webcite
• [33]Ragsdale DS, Avoli M: Sodium channels as molecular targets for antiepileptic drugs. Brain Res Rev 1998, 26:16-28.
• [34]Osterhoudt KC, Penning TM: Drug Toxicity and Poisining. In The Parmacological Basis of Therapeutics. 12th edition. Edited by Bruton LL, Chanbner BA, Knollmann BC. McGraw-Hill; 2011:77.
• [35]Baynes RE: Veterinary Pharmacology and Therapeutics, Volume 1198. In Chemotherapy of Parasitic Diseases: Ectoparasiticides. 9th edition. Edited by Riviere JE, Papich MG, Adams HR. Ames, Iowa, USA: Wiley-Blackwell; 2009.
• [36]Page SW: Small Animal Clinical Pharmacology, Volume 232. In Antiparasitic Drugs. Edited by Maddison JE, Page SW, Church DB. Edinburgh: Saunders Elsevier; 2008.
• [37]Giguere S: Antimicrobial Therapy in Veterinary Medicine, Volume 8. In General Principles of Antimicrobial Therapy. Edited by Giguere S, Prescott JF, Baggot JD, Walker RD, Dowling PM. Ames, Iowa, USA: Blackwell Publishing; 2006.
• [38]Chun R, Garrett LD, Vail DM: Small Animal Clinical Oncology. In Cancer Chemotherapy. Edited by Withrow SJ, Vail DM. St. Louis, Missouri, USA: Saunders Elsevier; 2007:163-192.
• [39]Vais H, Williamson MS, Goodson SJ, Devonshire AL, Warmke JW, Usherwood PN, Cohen CJ: Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations. J Gen Physiol 2000, 115(3):305-318.
• [40]Fourie JJ, Horak IG, Stanneck D: Efficacy of slow-release collar formulations of imidacloprid/flumeththrin and deltamethrin, and of spot-on formulations of fipronil/(s) - methoprene, dinotefuran/pyriproxyfen/permethrin and (s) - methoprene/amitraz/fipronil against Rhipicephalus sanguineus and Ctenocephalides felis felis on dogs. Parasite Vector 2012. Under review