EFFICACY AGAINST PARASITES
Type of action: Anthelmintic endoparasiticide, and ectoparasiticide
Main veterinary parasites controlled: liver flukes, certain gastrointestinal roundworms (= nematodes), various myiases (= parasitic maggots)
Efficacy against a specific parasite depends on the delivery form and on the dose administered. National regularory authorities determine whether a product is approved for a given indication, i.e. use on a particular host at a specific dose and against a specific parasite. Check the labels of the products available in your country.
Click here for general information on features and characteristics of PARASITICIDES.
Oral LD50, rat, acute*: 342 mg/kg
Dermal LD50, rat, acute*: not found
* These values refer to the active ingredient. Toxicity has to be determined for each formulation as well. Formulations are usually significantly less toxic than the active ingredients.
MRL (maximum residue limit) established for either beef, mutton pork or chicken meat*:
- CODEX: Yes
- EU: Yes
- USA: No
- AUS: Yes
* This information is an indicator of the acceptance of an active ingredient by the most influential regulatory bodies for use on livestock.
Withholding periods for meat, milk, eggs, etc. depend on delivery form, dose and national regulations. Check the product label in your country.
Learn more about closantel safety (poisoning, intoxication, overdose, antidote, symptoms, etc.).
It is obvious that veterinary products are not intended for and should never be used on humans!!!
MARKETING & USAGE
Decade of introduction: 1970
Introduced by: JANSSEN
Some original brands: FLUKIVER, SUPAVERM, SEPONVER
Patent: Expired (Particular formulations may be still patent-protected)
Use on LIVESTOCK: Yes, abundant in ruminants
Use on DOGS and CATS: No
Main delivery forms:
Use in human medicine: No
Use in public/domestic hygiene: No
Use in agriculture: No
Generics available: Yes, a lot
On livestock: Yes, reported for Haemonchus worms in sheep.
Closantel is a real endectocide, i.e. a compound that controls several endoparasites and ectoparasites at the usual therapeutic dose. However it is only a narrow-spectrum and not a broad-spectrum endectocide such as the macrocyclic lactones. Closantel is the most used salicylanilide.
It is used moderately in cattle, sheep and goats, mainly in the form of drenches and injectables, and there are a few pour-ons as well. Although it is a veteran anthelmintic, its use is increasing because it is often a valid alternative where resistance of gastrointestinal roundworms (to benzimidazoles, macrocyclic lactones, and/or levamisole) or liver flukes (to benzimidazoles) is a problem.
In contrast with many other anthelmintics (e.g. imidazothiazoles, benzimidazoles, tetrahydropyrimidines), closantel has a residual effect, i.e. it not only kills the parasites present in the host at the time of treatment, but protects against re-infestation for a period of time (up to several weeks) that depends on the dose and the specific parasite.
Closantel is not used on dogs and cats.
Efficacy of closantel
Closantel is highly effective against adults and larvae (6 to weeks old) of liver flukes (Fasciola hepatica), and against several important gastrointestinal roundworms (e.g. Bunostomum, Haemonchus, Oesophagostomum, Ostertagia - Teladorsagia, Strongyloides, Trichostrongylus), as well as against screwworms (maggots of Cochliomyia spp and Chrysomya spp), sheep nasal bots (Oestrus ovis), and sheep keds (Melophagus ovinus).
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 feces, >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 molting. Its inhibition interrupts their development to adult worms.