Closantel Base

Product Name: Closantel Base

pharmacokinetics of closantel:

After oral administration closantel is readily absorbed into the bloodstream. Four days after treatment up to 60%of the injected and 30% of the drenched closantel is absorbed to blood. In the blood, unchanged closantel binds strongly and almost completely (>99%) to plasma albumins. Peak plasma levels are reached 10 to 48 hours after administration, both after oral or intramuscular administration. Half-life in plasma is 3 to 4 weeks. Due to the strong binding to plasma albumins, closantel residues in the tissues are rather low; the highest ones were found in the lungs and the kidneys. Closantel is poorly metabolized. About 80% of the administered dose is excreted through the faces, >98% in the form of the parent molecule. Excretion 48 hours after oral administration reached ~45% of the administered dose, but only ~10% after intramuscular injection. Excretion half-life in the organism is 2 to 3 weeks.

In dairy cows about 1% of the administered dose is excreted unchanged through the milk. Influence of the diet. In ruminants, fasting slows the passage of food through the stomach and the gut, which increases the time for absorption of closantel into blood and hence its plasma concentration and bioavailability. Consequently, it is recommended to keep healthy animals off food for up to 24 hours before treatment with closantel. This should not be done with heavy pregnant, stressed, or weak animals. Fasting animals should have access to drinking water.

Mechanism of action of closantel:
The molecular mode of action of salicylanilides, including closantel, is not completely elucidated. They all are uncouplers of the oxidative phosphorylation in the cell mitochondria, which disturbs the production of ATP, the cellular "fuel". This seems to occur through suppression of the activity of succinate dehydrogenase and fumarate reductase, two enzymes involved in this process. This impairs the parasites motility and probably other processes as well. It seems that closantel also disturbs the liquid and ion transport mechanisms in the parasites membranes.Recently it has been discovered that closantel also inhibits chitinase in  Onchocerca  volvulus, a filarial nematode
causing river blindness in humans. Chitinase is an enzyme involved in larval melting. Its inhibition interrupts their development to adult worms.