Doramectin is a new fermentation-derived antiparasitic agent which belongs to the avermectin class, and is closely related structurally to ivermectin. Both compounds share a wide spectrum of antiparasitic activity and produce a similar paralysis in nematodes and parasitic arthropods. Whilst it is not possible to assign a single mode of action to the avermectins, it is likely that the entire series share a common mechanism. In parasitic organisms the effect is mediated through a specific avermectin binding site. The physiological response to avermectin binding is an increase in membrane permeability to chloride ions. In invertebrate nervous tissue an influx of chloride ions into the excitatory motor neurone in nematodes or muscle cell of arthropods results in hyperpolarisation and the elimination of signal transmission with resulting paralysis.
Doramectin is exceptionally well-tolerated in mammals, where receptor/channel complexes are localised in the CNS. Poor penetration of large molecular weight compounds, such as avermectins, through the blood-brain barrier suggests that high systemic concentrations would be required before neurological function is affected.
Pharmacokinetic particulars
Maximum plasma concentration of doramectin occurs in cattle 3 days after subcutaneous administration of Dectomax Solution for Injection. In sheep the maximum plasma concentration of doramectin occurs 2 days after intramuscular administration of Dectomax Solution for Injection; in pigs 3 days after intramuscular administration. An elimination half-life of around 6 days for cattle, by the subcutaneous route, and 4.5 days for sheep, by the intramuscular route, results in sustained doramectin concentrations which protect cattle and sheep from parasitic infection and re-infection for extended periods following treatment.
Environmental properties
Like other macrocyclic lactones, doramectin has the potential to adversely affect non-target organisms. Following treatment, excretion of potentially toxic levels of doramectin may take place over a period of several weeks. Faeces containing doramectin excreted onto pasture by treated animals may reduce the abundance of dung feeding organisms which may impact on the dung degradation.
Doramectin is very toxic to aquatic organisms and may accumulate in sediments.