Closantel

BRAND NAMES

Brand names for Closantel include EXINOT, Tricloz Oral Solution, Zontel Plus, Solantel, Closavir, and Zycloz Bolus. Some formulations are also marketed under the generic name Closantel Sodium.

• EXINOT: The first Closantel 15% oral solution developed in India.

• Tricloz Oral Solution: A brand of Closantel 15% oral formulation.

• Zontel Plus: A combination product containing Closantel and Ivermectin.

• Solantel: A veterinary formulation available in various countries.

• Closavir: A Closantel 15% veterinary oral solution.

• Zycloz Bolus: A bolus formulation containing Closantel.

• Generic names: Some products are marketed simply as Closantel Sodium by different manufacturers.

MECHANISM OF ACTION

It acts as a proton ionophore, uncoupling mitochondrial oxidative phosphorylation in the parasite's cells. This disruption inhibits the synthesis of ATP (adenosine triphosphate), the cellular "fuel," leading to a change in the parasite's energy metabolism and subsequent death. It also appears to disrupt ion transport mechanisms in parasite membranes and inhibit the chitinase enzyme in some parasites, which is crucial for larval molting.

PHARMACOKINETICS

Absorption:

Closantel is moderately absorbed after oral or subcutaneous administration. Oral bioavailability is around 30–50% in ruminants. Peak plasma concentrations are generally reached within 24–48 hours after dosing.

Distribution:

Closantel binds extensively to plasma proteins, especially albumin (over 99%), leading to a long plasma half-life. It is widely distributed in body tissues but tends to concentrate in the liver, kidneys, and gastrointestinal tract.

Metabolism:

Metabolism of Closantel is limited; most of the drug remains unchanged in the body. Only a small fraction undergoes hepatic biotransformation.

Excretion:

Closantel is excreted slowly, primarily through bile and feces. A minor portion is eliminated via urine. Due to its strong protein binding, the elimination half-life is long—ranging from 2 to 3 weeks in ruminants.

PHARMACODYNAMICS

Closantel is a halogenated salicylanilide anthelmintic that acts mainly against blood-feeding parasites such as Haemonchus contortus and Fasciola hepatica. It works by uncoupling oxidative phosphorylation in parasite mitochondria, leading to depletion of energy (ATP) and subsequent paralysis and death of the parasite. Closantel also disrupts parasite motility and causes changes in tegumental structure, impairing survival.

ADMINISTRATION

Closantel can be administered orally (as a drench or bolus) or parenterally (subcutaneous injection), depending on the formulation. Oral administration is common for herd treatment, while injections may be used for individual animals requiring rapid action.

DOSAGE AND STRENGTH

• Oral solutions (Closantel 15%): Typically dosed at 5–10 mg/kg body weight for sheep and cattle.

• Injectable formulations (Closantel 5% or 10%): Administered subcutaneously at similar dose rates depending on the species and severity of infection.

• Bolus formulations: Designed for slow release and prolonged effect in cattle.

The exact dosage depends on the formulation and target parasite species, so veterinary guidance is essential.

DRUG INTERACTIONS

Closantel should not be combined with other drugs that strongly bind to plasma proteins (e.g., other salicylanilides) to avoid toxicity. Caution is advised when used with other antiparasitic agents such as ivermectin or levamisole, as additive effects may occur.

FOOD INTERACTIONS

Feeding does not significantly affect the absorption of Closantel, although administering it with feed or after grazing can improve tolerance and reduce gastrointestinal irritation. Withdrawal periods for meat and milk must be strictly followed after treatment.

CONTRAINDICATIONS

Closantel is contraindicated in animals with severe liver or kidney disease, and in those hypersensitive to Closantel or related compounds. It should not be administered to non-ruminant species (e.g., dogs or horses), as toxicity may occur.

SIDE EFFECTS

• Temporary loss of appetite or mild lethargy after dosing

• Rarely, eye or neurological disorders at high doses (e.g., blindness, incoordination)

• Local irritation at the injection site (for injectable forms)

OVERDOSE

Overdose can lead to signs of toxicity, including blindness, depression, ataxia, excessive salivation, and weakness. High plasma concentrations cause damage to the optic nerve and CNS. There is no specific antidote; treatment is supportive, including fluids and symptomatic care.

TOXICITY

Closantel has a narrow safety margin, especially in young or weak animals. Toxicity results from **disruption of oxidative metabolism in host tissues at excessive doses. Acute or chronic overdose may cause optic nerve degeneration, hepatic injury, or renal damage. Proper dosing, based on body weight and species, is crucial to avoid adverse effects