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Lufenuron is a drug that inhibits chitin synthesis. It is categorized as a benzoylphenyl urea (also known as BPU or Benzoylurea).[1][2] It was first introduced in the United States in 1990 as a public health insecticide for controlling fleas on pet animals,[1][3][4] and on field crops.[3] It is regarded as an insect growth regulator (IGR), specifically in the insect development inhibitor (IDI) category. Lufenuron is one of the two active ingredients in the drug Milbemycin oxime/lufenuron (marketed as Sentinel), which targets fleas and heartworms in animals.[3]
Function
[edit]The function of lufenuron is to disrupt the life cycle of developing fleas to prevent larval flea growth.[5] Lufenuron is stored in the adipose tissue of animals and transferred to adult fleas when the flea feeds on a treated animal.[1][3][6] Adult female fleas transfer lufenuron to their eggs through their blood.[1] Once in the egg, lufenuron causes degeneration of epidermal cells responsible for synthesizing chitin,[1][4] inhibiting the production of chitin.[4] Larval development in the egg is weakened in a way that it cannot withstand hemolymph pressure and muscular movement during the time of moulting,[4][6] making the egg infertile.[5] Death of the flea larvae occurs within the egg or during any of the moult stages in its life cycle.[6] Although some eggs may hatch larvae, they can not survive because the flea feces that the hatched larvae will feed on contain a sufficient amount of lufenuron to prevent growth.[3] Lufenuron does not directly kill adult fleas.[5]
Clinical Administrations and Treatments
[edit]Lufenuron can be applied through oral administration or injection administration. For oral administration, it should be provided monthly,[4] at a dose of 10 mg/kg in dogs and 30 mg/kg in cats.[3][6] Oral administration should be taken with food for appropriate stomach absorption of the drug.[1] If a dose is taken in the absence of food, drug absorption is reduced and rapid drug elimination follows, resulting in a less effective dose.[6] For injection administration, it should be provided once every six months at a dose of 10 mg/kg in cats and dogs. An injected dose of lufenuron results in a decrease in emergence of adult fleas from eggs for up to 196 days.[1][4]
Although lufenuron usually has little to no effect on adult fleas, prolonged feeding of an adult flea on a lufenuron-treated animal can result in cuticle deposition in the adult flea, leading to increased mortality rates.[4] It is recommended to supplement lufenuron treatment with an adulticide within the first 21 days of lufenuron treatment to eradicate existing adult flea populations.[4][5]
Few adverse reactions have been reported in dogs and cats when the normal dosage of lufenuron treatment is applied. In cases of eye exposures, eyes should be thoroughly washed with water, and treated with fluorescein dye or slit-lamp examination in severe cases. In cases of hypersensitivity reactions, the animal should be bathed in non-insecticidal shampoo.[3]
Resistance
[edit]Lufenuron resistance has been shown in cat fleas. Surviving fleas from lufenuron allow the cells of fleas to become continually exposed to the drug, which can result in some lufenuron-resistant flea populations.[7]
Lufenuron resistance has been shown in natural populations of Drosophila melanogaster. The mechanism responsible for resistance is accredited to the overexpression of specific cytochrome P450 (also known as CYP) enzymes that increases drug metabolism of lufenuron, resulting in an ineffective dose of lufenuron.[8]
Other Types of Infections Treated
[edit]Dermatophytosis
[edit]Oral administration of lufenuron is also used in dogs and cats for the treatment of the fungal infection, dermatophytosis, also known as ringworm infection. Since fungal cell walls are partly made of chitin, the use of lufenuron on this fungal infection has been shown to be effective in dogs and cats.[9] The recommended drug dose for treating dermatophytosis is 80-100 mg/kg once per two weeks, until complete recovery. On average, recovery in dogs and cats range from 12-90 days, although some argue that lufenuron has little to no effect on the process of recovery. In terms of prevention, lufenuron slows the establishment of dermatophytosis, but does not prevent or alter the infection process.[10]
References
[edit]- ^ a b c d e f g Taylor, M.A. (May 2001). "Recent Developments in Ectoparasiticides". The Veterinary Journal. 161 (3): 253–268. doi:10.1053/tvjl.2000.0549.
{{cite journal}}:|access-date=requires|url=(help) - ^ Mueller, Ralf S. (April 2004). "Treatment protocols for demodicosis: an evidence-based review". Veterinary Dermatology. 15 (2): 75–89. doi:10.1111/j.1365-3164.2004.00344.x.
{{cite journal}}:|access-date=requires|url=(help) - ^ a b c d e f g Hovda, LR; Hooser, SB (March 2002). "Toxicology of newer pesticides for use in dogs and cats". The Veterinary clinics of North America. Small animal practice. 32 (2): 455–467. PMID 12012747.
{{cite journal}}:|access-date=requires|url=(help) - ^ a b c d e f g h Rust, M (May 2005). "Advances in the control of (cat flea) on cats and dogs". Trends in Parasitology. 21 (5): 232–236. doi:10.1016/j.pt.2005.03.010.
{{cite journal}}:|access-date=requires|url=(help) - ^ a b c d Carlotti, Didier N.; Jacobs, Dennis E. (June 2000). "Therapy, control and prevention of flea allergy dermatitis in dogs and cats". Veterinary Dermatology. 11 (2): 83–98. doi:10.1046/j.1365-3164.2000.00204.x.
{{cite journal}}:|access-date=requires|url=(help) - ^ a b c d e Shipstone, Michael A.; Mason, Kenneth V. (September 1995). "The Use of Insect Development Inhibitors as an Oral Medication for the Control of the Fleas Ctenocephalides felis, Ct. canis in the Dog and Cat". Veterinary Dermatology. 6 (3): 131–137. doi:10.1111/j.1365-3164.1995.tb00056.x.
{{cite journal}}:|access-date=requires|url=(help) - ^ Bossard, Robert L.; Hinkle, Nancy C.; Rust, Michael K. (July 1998). "Review of insecticide resistance in cat fleas (Siphonaptera: Pulicidae)". Journal of medical entomology. 35 (4): 415–422. PMID 9701921.
{{cite journal}}:|access-date=requires|url=(help) - ^ Bogwitz, M. R.; Chung, H.; Magoc, L.; Rigby, S.; Wong, W.; O'Keefe, M.; McKenzie, J. A.; Batterham, P.; Daborn, P. J. (24 August 2005). "Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster". Proceedings of the National Academy of Sciences. 102 (36): 12807–12812. doi:10.1073/pnas.0503709102.
{{cite journal}}:|access-date=requires|url=(help) - ^ Ben-Ziony, Yair; Arzi, Boaz (November 2000). "Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999)". Journal of the American Veterinary Medical Association. 217 (10): 1510–1513. doi:10.2460/javma.2000.217.1510.
{{cite journal}}:|access-date=requires|url=(help) - ^ Moriello, Karen A. (April 2004). "Treatment of dermatophytosis in dogs and cats: review of published studies". Veterinary Dermatology. 15 (2): 99–107. doi:10.1111/j.1365-3164.2004.00361.x.
{{cite journal}}:|access-date=requires|url=(help)