Moxidectin is an endectocide active against a wide range of internal and external parasites and is a second generation macrocyclic lactone of the milbemycin family. Its principal mode of action is interfering with neuromuscular transmission of the GABA (gamma amino butyric acid)-gated or glutamate-gated chloride channels. Moxidectin stimulates the release of GABA and increases its binding to the postsynaptic receptors, and binds to the glutamate-gated chloride channels. The net effect is to open the chloride channels on the postsynaptic junction to allow the inflow of chloride ions and induce an irreversible resting state. This results in flaccid paralysis and eventual death of parasites exposed to the drug.

Triclabendazole is a flukicide belonging to the benzimidazole group of anthelmintics. It is well established that benzimidazole anthelmintics selectively bind to β-tubulin, thus causing the depolymerisation of microtubules and the subsequent disruption of microtubule-based processes in helminths.

Moxidectin is distributed throughout the body tissues but due to its lipophilicity the highest drug concentrations are obtained in fat tissue. Moxidectin undergoes biotransformation by hydroxylation. The only significant route of excretion is the faeces. The main pharmacokinetic parameters of moxidectin when administered as pour-on in the final combined formulation of this product were the following: AUClast 50.9 ng.d.mL-1, Cmax 4.69 ng.mL-1, Tmax 8.7 d, MRT 10.74 d.

The majority of the oral dose of triclabendazole in rats, sheep, goats and rabbits is eliminated in faeces after 6-10 days, as unchanged drug or products of biliary excretion. Urinary excretion is minimal. Sulphone, sulphoxide, ketone and 4-hydroxy triclabendazole derivatives are the main metabolites identified in plasma. Plasma kinetic studies of sulfoxide and sulfone derivatives in various species after oral administration showed the sulfoxide to predominate in rabbits, sheep and humans, and the sulfone in the horse, dog and cattle. The main pharmacokinetic parameters of triclabendazole sulfoxide when administered in the final combined formulation of this product were: AUClast 26.9 µg.h.mL-1, Cmax 2.92 µg.mL-1, Tmax 3.3 d, MRT 9.72 d. The main pharmacokinetic parameters of triclabendazole sulfone when administered in the final combined formulation were: AUClast 110.2 µg.h.mL-1, Cmax 7.78 µg. mL-1, Tmax 12.9 d, MRT 12.98 d .

Moxidectin fulfils the criteria for a (very) persistent, bioaccumulative and toxic (PBT) substance. In particular, in acute and chronic toxicity studies with algae, crustaceans and fish, moxidectin showed toxicity to these organisms, yielding the following endpoints:

Organism		EC50	NOEC
Algae	S. capricornutum	>86.9 μg/l	86.9 μg/l
Crustaceans (Water fleas)	Daphnia magna (acute)	0.0302 μg/l	0.011 μg/l
	Daphnia magna (reproduction)	0.0031 μg/l	0.010 μg/l
Fish	O. mykiss	0.160 μg/l	Not determined
	L. macrochirus	0.620 μg/l	0.52 μg/l
	P. promelas (early life stages)	Not applicable	0.0032 μg/l
	Cyprinus carpio	0.11 μg/l	Not determined

EC50: the concentration which results in 50% of the test species individuals being adversely affected, i.e. both mortality and sub-lethal effects.

NOEC: the concentration in the study at which no effects are observed.

This implies that when allowing moxidectin to enter water bodies, this may have a severe and lasting impact on aquatic life. To mitigate this risk, all precautions for use and disposal must be adhered to.