• 1

    Blair LS, Campbell WC. Efficacy of ivermectin against Dirofilaria immitis larvae in dogs 31, 60 and 90 days after infection. Am J Vet Res 1980;41:2108.

    • Search Google Scholar
    • Export Citation
  • 2

    McCall JW. The safety-net story about macrocyclic lactone heartworm preventives: a review, an update and recommendations. Vet Parasitol 2005;133:197206.

    • Search Google Scholar
    • Export Citation
  • 3

    McCall JW, Dzimianski MT & Plue RE, et al. Ivermectin in heartworm prophylaxis: study with experimentally induced and naturally acquired infections. In:Otto GF, ed.Proceedings of the Heartworm Symposium '86. Washington, DC: American Heartworm Society, 1986;913.

    • Search Google Scholar
    • Export Citation
  • 4

    Grieve RB, Frank GR & Stewart VA, et al. Chemoprophylactic effects of milbemycin oxime against larvae of Dirofilaria immitis during prepatent development. Am J Vet Res 1991;52:20402042.

    • Search Google Scholar
    • Export Citation
  • 5

    McCall JW, McTier TL & Holmes RA, et al. Prevention of naturally acquired heartworm infection in heartworm-naïve beagles by oral administration of moxidectin at an interval of either one or two months. In:Soll MD, ed.Proceedings of the Heartworm Symposium '92. Batavia, Ill: American Heartworm Society, 1992;169177.

    • Search Google Scholar
    • Export Citation
  • 6

    McTier TL, McCall JW & Jernigan AD, et al. UK-124,114, a novel avermectin for the prevention of heartworms in dogs and cats. In:Seward RL, Knight DH, ed.Proceedings of the Heartworm Symposium '98. Batavia, Ill: American Heartworm Society, 1998;187192.

    • Search Google Scholar
    • Export Citation
  • 7

    Genchi C, Poglayen G & Kramer LH, et al. Efficacy of moxidectin for the prevention of adult heartworm (Dirofilaria immitis) infection in dogs. Parassitologia 2001;43:139141.

    • Search Google Scholar
    • Export Citation
  • 8

    Heaney K, Lindahl RG. Safety evaluation of moxidectin sustained-release injectable in 10-week-old puppies. Vet Parasitol 2005;133:227231.

    • Search Google Scholar
    • Export Citation
  • 9

    Clark SL, Crowley AJ & Schmidt PG, et al. Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs. Am J Vet Res 2004;65:752757.

    • Search Google Scholar
    • Export Citation
  • 10

    Maeda H, Brandon M, Sano A. Design of controlled-release formulation for ivermectin using silicone. Int J Pharm 2003;261:919.

  • 11

    Kajihara M, Sugie T & Hojo T, et al. Development of a new drug delivery system for protein drugs using silicone (II). J Control Release 2001;73:279291.

    • Search Google Scholar
    • Export Citation
  • 12

    Bourget P, Delouis JM. Review of a technique for the estimation of area under the concentration curve in pharmacokinetic analysis. Therapie 1993;48:15.

    • Search Google Scholar
    • Export Citation
  • 13

    Daurio CP, Cheung En & Jeffcoat AR, et al. Bioavailability of ivermectin administered orally to dogs. Vet Res Comm 1992;16:125130.

  • 14

    Lok JB, Knight DH & Wang GT, et al. Activity of an injectable, sustained-release formulation of moxidectin administered prophylactically to mixed-breed dogs to prevent infection with Dirofilaria immitis. Am J Vet Res 2001;62:17211726.

    • Search Google Scholar
    • Export Citation
  • 15

    McCall JW, Lindemann BA, Porter CA. Prophylactic activity of avermectins against experimentally induced Dirofilaria immitis infection in dogs. In:Otto GF, ed.Proceedings of the Heartworm Symposium '80. Edwardsville, Kan: Veterinary Medicine Publishing Co, 1981;126130.

    • Search Google Scholar
    • Export Citation
  • 16

    Nelson CT, McCall JW & Rubin SB, et al. 2005 guidelines for the diagnosis, prevention and management of heartworm (Dirofilaria immitis) infection in dogs. Vet Parasitol 2005;133:255266.

    • Search Google Scholar
    • Export Citation
  • 17

    Cummings J, Vickers L, Marbaugh J. Evaluation of veterinary dispensing records to measure “clinic compliance” with recommended heartworm prevention programs. In:Soll MD, Knight DH, ed.Proceedings of the Heartworm Symposium '95. Batavia, Ill: American Heartworm Society, 1995;183186.

    • Search Google Scholar
    • Export Citation
  • 18

    Pulliam JD, Seward RL & Henry RT, et al. Investigating ivermectin toxicity in Collies. Vet Med 1985;80:3340.

  • 19

    Mealy KL, Bentjen SA & Gay JM, et al. Ivermectin sensitivity in Collies is associated with a deletion mutation of the MDR1 gene. Pharmacogenetics 2001;11:727733.

    • Search Google Scholar
    • Export Citation

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Evaluation of a covered-rod silicone implant containing ivermectin for long-term prevention of heartworm infection in dogs

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  • 1 Smart Drug Systems Inc, Ste 102, 181 S Broad St, Pawcatuck, CT 06379.
  • | 2 Smart Drug Systems Inc, Ste 102, 181 S Broad St, Pawcatuck, CT 06379.
  • | 3 School of Pharmacy, University of Tasmania, Hobart, Tasmania 7001, Australia.
  • | 4 Smart Drug Systems Inc, Ste 102, 181 S Broad St, Pawcatuck, CT 06379.
  • | 5 Smart Drug Systems Inc, Ste 102, 181 S Broad St, Pawcatuck, CT 06379.

Abstract

Objective—To evaluate use of covered-rod (CR) silicone implants containing ivermectin for long-term prevention of infection with Dirofilaria immitisin dogs.

Animals—145 adult male and female dogs.

Procedures—Dogs received implants of different sizes, and ivermectin concentrations and serum ivermectin concentrations were monitored for 16, 57, and 56 weeks, respectively, in 3 preclinical dose selection studies. Ability of implants to prevent infection with D immitis was evaluated in 2 further studies; dogs were challenged with 50 infective third-stage larvae 52 weeks after implant administration and necropsied 145 days after challenge, and the total number of adult heartworms was counted. A field study was then undertaken in which client-owned dogs received an implant and plasma samples were collected at intervals until week 52 for ivermectin analysis and heartworm antigen determination.

Results—Use of the implants resulted in maintenance of an ivermectin concentration ≥ 0.2 ng/mL for 12 months. In challenge studies, no treated dogs had adult heartworms, in contrast to untreated dogs, which all had adult heartworms at necropsy. In the field study, dogs treated with an implant had negative results of heartworm antigen testing for 12 months.

Conclusions and Clinical Relevance—The CR silicone implant containing 7.3 mg of ivermectin was 100% effective in preventing experimental infection with D immitislarvae and resulted in negative results for heartworm antigen in a field trial. This product has the potential to alleviate poor owner compliance with monthly prevention regimens.

Abstract

Objective—To evaluate use of covered-rod (CR) silicone implants containing ivermectin for long-term prevention of infection with Dirofilaria immitisin dogs.

Animals—145 adult male and female dogs.

Procedures—Dogs received implants of different sizes, and ivermectin concentrations and serum ivermectin concentrations were monitored for 16, 57, and 56 weeks, respectively, in 3 preclinical dose selection studies. Ability of implants to prevent infection with D immitis was evaluated in 2 further studies; dogs were challenged with 50 infective third-stage larvae 52 weeks after implant administration and necropsied 145 days after challenge, and the total number of adult heartworms was counted. A field study was then undertaken in which client-owned dogs received an implant and plasma samples were collected at intervals until week 52 for ivermectin analysis and heartworm antigen determination.

Results—Use of the implants resulted in maintenance of an ivermectin concentration ≥ 0.2 ng/mL for 12 months. In challenge studies, no treated dogs had adult heartworms, in contrast to untreated dogs, which all had adult heartworms at necropsy. In the field study, dogs treated with an implant had negative results of heartworm antigen testing for 12 months.

Conclusions and Clinical Relevance—The CR silicone implant containing 7.3 mg of ivermectin was 100% effective in preventing experimental infection with D immitislarvae and resulted in negative results for heartworm antigen in a field trial. This product has the potential to alleviate poor owner compliance with monthly prevention regimens.

Contributor Notes

Supported by Smart Drug Systems Incorporated.

Address correspondence to Dr. Martinod.