Pharmacotherapeutic group: Endectocides (milbemycins)
ATCvet code: QP54AB02
Pharmacodynamic properties
Moxidectin is a parasiticide active against a wide range of economically important 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. 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
Resistance to moxidectin is mediated in part by membrane transporter P-glycoproteins, and cross resistance with other macrocyclic lactones is possible.
Pharmacokinetic particulars
22% of an oral dose of moxidectin is absorbed with maximum blood concentrations being achieved 9 hours post treatment. The drug is distributed throughout the body tissues but due to its lipophilicity the target tissue is fat where concentrations are 10 to 20 times higher than those found in other tissues. The depletion half life in fat is 23-28 days.
Moxidectin undergoes limited biotransformation by hydroxylation. The only significant route of excretion is the faeces.
Environmental properties
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.