Pharmacotherapeutic Group: Ivermectin, combinations.
ATC Vet Code: QP54AA51
Pharmacodynamic Properties
Ivermectin is an endectocide with activity against a wide range of internal and external parasites. Ivermectin is a macrocylic lactone and acts by inhibiting nerve impulses. 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 hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the relevant parasites. 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 macrocylic lactones have a low affinity for other mammalian ligand-gated chloride channels and they do not readily cross the blood-brain barrier.
Closantel is a member of the salicylanilide class of anthelmintics. Salicylanilides are hydrogen (proton) ionophores (referred to as oxidative phosphorylase uncouplers.)
The chemical structure of salicylanilides illustrate the possession of a detachable proton. This type of molecule is lipophilic and is known to shuttle protons across membranes, in particular the inner mitochondrial membrane. Closantel acts by uncoupling oxidative phosphorylation.
Closantel is a parasiticide with flukicide activity and efficacy against certain other helminths and arthropods.
Pharmacokinetic Properties
After topical administration of Closamectin Pour-On to cattle at a dose rate of 500 µg ivermectin per kg and 20 mg closantel per kg the following parameters were observed: Ivermectin – Cmax of 19.13 ng/mL and AUC of 2440 ng.hr/mL; Closantel – Cmax of 68.5 µg/mL and AUC of 35207 µg.hr/mL.
Ivermectin is only partially metabolised. In cattle, only about 1 to 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 degradation products. Salicylanilides are poorly metabolised and are excreted mainly unchanged. About 90% of closantel is excreted unchanged in the faeces and urine in cattle.