Ivermectin release

Ivermectin is widely used as an endectocide for catde as an injectable, oral, topical, or slow release bolus for sheep as an injectable or oral formulation for swine as an injectable for horses as a paste or drench and for goats as an injectable or oral formulation. Ivermectin has recently been introduced for heartworm prophylaxis in dogs and it is being studied for use with cats, many other mammals, birds, fish, and reptiles. 

The average daily release rate of ivermectin increases modestly during the steady-state period. This is most likely the result of a combination of factors... 

DG Pope, PK Wilkinson, JR Egerton, J Conroy. Oral controlled release delivery of ivermectin in cattle via an osmotic pump. J Pharm Sci 74 1108-1110, 1985. 

JR Egerton, D Suhayda, CH Eary. Prophylaxis of nematode infections in cattle with an indwelling, ruminoreticular ivermectin sustained release bolus. Vet Parasitol 74 614-617, 1986. 

Yeates, G., Dimander, S.-O., Waller Peter, J. and Hoglund, J. (2003). Soil nematode populations beneath faecal pats from grazing cattle treated with the ivermectin sustained-release bolus or fed the nematophagous fungus Duddingtonia flagrans to control nematode parasites . Acta Agricultural Scandinavica, Section A, Animal Science, 53, 197-206. 

Controlled-release ruminal bolus Ivermectin Cattle P.O. 

Controlled-release ruminal capsule Ivermectin Sheep P.O. 

Avermectin (Ivermectin) (Doramectin) (Abamectin) (Eprinomectin) Mites, lice, Horn fly. Warble-fly larvae Solution (pour on) Parenteral solution (S.C. injection) Controlled-release ruminal bolus (ivermectin)... 

Baggott, D.G. Ross, D.B. Preston, J.M. Gross, S.J. Nematode burdens and productivity of grazing cattle treated with a prototype sustained-release bolus containing ivermectin. Vet. Rec. 1994, 135, 503-506. 

A role for the release of Wolbachia bacterial endosym-bionts has been suggested in the pathogenesis of the Mazzotti reaction (SEDA-26, 345). There was a good correlation between Wolbachia DNA, serum TNF-alfa, and the antibacterial peptides calprotectin and calgranu-lin after treatment with ivermectin or diethylcarbamazine, supporting a role for Wolbachia products in mediating these inflammatory responses (27). 

There are diverse formulations and delivery systems for macrocylic lactones in ruminants, including injectable, oral, sustained-release bolus and transdermal ("pour on") products. In Europe, it is popular clinical practice to administer injectable solutions of ivermectin intravenously (i.v.) to horses. This constitutes extra-label (unlicensed) use and there are no objective data to support the perceived improved efficacy following administration by this route. Specifically, in relation to hypobiotic cyathostome larvae, Klei et al (1993) reported no increase in efficacy when horses were administered 10 pg/kg, which is five times the recommended dose rate. 

Fig. 2.6 Technological design of (a) controlled-release ruminal bolus containing ivermectin for administration to cattle and (b) controlled-release ruminal capsule containing albendazole or ivermectin for administration to sheep. (Reproduced with permission from Klink et at. (1998).)...

Recently a slow release bolus of ivermectin has been found to be more than 99% effective against trichostrongyles and other gastrointestinal nematodes in grazing animals [129,130]. Consequently it has been suggested that treatment of cattle with ivermectin is economical as it keeps them free of helminths leading to better output of animal products [131]. 

The paralysing action of ivermectin on the nematodes is due to its ability to activate a membrane chloride conductance in neurons of the nerve cord either directly or by enhancing the presynaptic release of GABA [180, 189] which eventually results in opening of chloride channels. 

Figure 7. Ivermectin- and milbemycin-stimulated release of neurotransmitter from cockroach central nerve terminals in superfusion.

Figure 8. The inhibition of ivermectin-dependent release of label from synaptosomes by selected chloride channel antagonists.

Figure 9. The lack of effect of TBPS on ivermectin-induced release of transmitter from cockroach synaptosomes. (Compounds added at arrow).

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