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Pharmacological particulars
Pharmacotherapeutic group: Endectocide. ATC vet code: QP54AA01.
Pharmacodynamic properties
Ivermectin is a member of the macrocyclic lactone class of endectocides which have a unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and 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 Properties
Maximum plasma concentration:
At a dose level of 0.2mg ivermectin per kg a maximum plasma concentration of 35-50ng/ml is reached in ± 2 days and the half-life in plasma is 2.8 days. It is also established that ivermectin is carried mainly in the plasma (80%). This distribution between plasma and blood cells remains relatively constant.
At a dose of 0.3mg ivermectin per kg an average peak of 16ng/ml is reached one day after injection
During trials carried out at a dose rate of 0.3mg ivermectin per pg bodyweight, peak plasma concentrations were reached in 3 (±0.5) days and the drug persisted in plasma for up to 28 days.
Excretion: Length of time and route
Only about 1-2% is excreted in the urine the remainder is excreted in the faeces, approximately 60% of which is excreted as unaltered drug. The remainder is excreted as metabolites or degredation products.
Radioactive ivermectin was administered to sheep as a dose rate of 0.3mg per kg. Analyses of the faeces showed that about 99% of the drug and its metabolites are excreted in the faeces, ±1% being excreted in the urine.
Biliary excretion is also the major route of ivermectin excretion in pigs.