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Pharmacological particulars
Pharmacodynamic properties
Eprinomectin is a member of the macrocyclic lactone class of endectocides. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve or muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite.
Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).
The margin of safety for compounds of this class is attributable to the fact that mammals do not have glutamate-gated chloride channels; the macrocyclic lactones have a low affinity for other mammalian ligand-gated chloride channels, and they do not readily cross the blood-brain barrier.
Pharmacokinetic particulars
Eprinomectin is bound extensively to plasma proteins (99%).
Pharmacokinetic studies have been conducted in lactating and non-lactating animals, administered topically at a single dosage of 0.5 mg/kg body weight in cattle and at 1 mg/kg bodyweight in sheep and goats.
For cattle, results from two representative studies found mean peak plasma concentrations of 9.7 and 43.8 ng/ml that were observed at 4.8 and 2.0 days post dose. The corresponding elimination half-lives in plasma were 5.2 and 2.0 days, and mean area-under-the-curve values of 124 and 241 ng*day/ml.
Eprinomectin is not extensively metabolized in cattle following topical administration.
Faeces was the major route of elimination of the drug in beef cattle and dairy cows.
For sheep, a mean peak plasma concentration (Cmax) of 6.20 ng/ml was observed following a topical dose of 1mg/kg. The half-life in plasma was 6.4 days with mean area under the curve (AUC last) value of 48.8 ng*day/ml.
For goats, peak mean plasma concentrations ranging from 3 to 13.1 ng/ml were observed from day 1 to day 2 post dose. The half life in plasma ranged from less than one day to 3 days with area under the curve mean values ranging from 15.7 to 39.1 ng-day/ml.
An in vitro microsomal metabolism study was conducted using liver microsomes isolated from cattle, sheep and goats. It showed that the differences in pharmacokinetics observed between cattle, sheep and goats do not result from differences in the rate or extent of metabolism but suggests more complete absorption of eprinomectin by cattle.