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Pharmacological particulars
Pharmacotherapeutic group: Endectocides, macrocyclic lactones, avermectins, ivermectin - combinations. ATC vet code: QP54AA51.
Pharmacodynamic properties
Ivermectin is a member of the macrocyclic lactone class of endectocides and has a unique mode of action. It has broad and potent antiparasitic activity. It binds 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 hyperpolarisation 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-amino-butyric 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, that the macrocyclic lactones have a low affinity for other mammalian ligand-gated chloride channels and they do not readily cross the blood-brain barrier.
Clorsulon is rapidly absorbed in the blood stream and is bound to the erythrocytes and plasma which are ingested by the fluke. Clorsulon inhibits the glycolytic enzymes in the fluke and deprives it of its main source of metabolic energy.
Pharmacokinetic properties
After subcutaneous administration of 2mg clorsulon and 0.2mg ivermectin per kg bodyweight, the plasma profile demonstrated a slow, steady absorption of ivermectin which reached a maximum plasma concentration at a median time of 1.50 days. In contrast, clorsulon appeared rapidly absorbed with a maximum plasma concentration at a median time of 0.25 days. The terminal half life for the two active ingredients were determined as follows: Ivermectin approximately 3.79 days and clorsulon approximately 3.58 days.