ATCvet code:
QP54AA51
Pharmacodynamics:
Avermectins, interact with glutamate-gated chloride ion channels, to increase the chloride ion permeability of the cell membrane, causing irreversible neuromuscular blockade in nematodes and arthropods, leading to paralysis and death of parasites. In nematodes, extensive research has indicated that common mechanisms of resistance against ivermectin include GluCl mutations, changes to ABC transporter expression, and through upregulation of detoxification genes. In arthropods in general, target-site resistance is a common mechanism of insecticide resistance. Selection of resistant isolates with ivermectin leads to cross-resistance to eprinomectin and moxidectin depending upon the underlying mechanism of resistance. Triclabendazole interferes with the intracellular transport mechanism of cells and inhibits protein synthesis. It is effective against liver fluke Fasciola. Possible mechanism(s) of resistance to triclabendazole that have been studied are: tubulin binding, altered drug uptake and modified drug metabolism, but the molecular basis for each of these possibilities has yet to be identified. So, it is likely that drug resistance in F. hepatica is polygenic in nature.
Pharmacokinetics:
Ivermectin is rapidly absorbed and reaches peak plasma concentration within 1 day. Afterwards plasma concentrations decrease with a half-life of 5 days. Triclabendazole is rapidly absorbed, oxidised to triclabendazole sulfoxide and triclabendazole sulfone. Peak plasma concentration is reached within 2 days.
Afterwards plasma concentration decreases, with a half-life of 1.5 days. Both metabolites bind strongly to plasma proteins, particularly albumin. More than 90% of the dose is excreted in the faeces, 2% in the urine and less than 1% in milk within 10 days. The inter-individual variability of the kinetics of ivermectin and metabolites of triclabendazole in ovine species is high.