Ivermectin's Action: What does ivermectin do inside the body?

October 8, 2025 •

5 min read

Ivermectin, a Nobel Prize-winning discovery, is a broad-spectrum antiparasitic agent widely used in both human and veterinary medicine. To understand its effects and safety, it is crucial to examine its mechanism of action. This article explains what does ivermectin do inside the body, focusing on its selective lethality to parasites while remaining relatively non-toxic to mammals.

Quick Summary

Ivermectin works by targeting and paralyzing specific chloride ion channels in the nerve and muscle cells of parasites, leading to their death. In mammals, it is generally non-toxic at standard therapeutic doses due to the presence of a blood-brain barrier and different ion channel structures.

Key Points

Paralyzes Parasites: Ivermectin binds to and opens specific chloride ion channels in parasite nerve and muscle cells, leading to paralysis and death.
Spares Mammals: In humans, therapeutic doses are non-toxic because the drug does not easily cross the blood-brain barrier due to the P-glycoprotein pump.
Treats Diverse Infections: It is effective against various parasitic worms causing intestinal strongyloidiasis and river blindness, as well as ectoparasites like scabies and lice.
Metabolized in the Liver: The drug is primarily processed by the liver and then eliminated through the feces.
Risk with Misuse: Taking large doses or unapproved veterinary formulations can lead to severe toxicity, including neurological symptoms, in humans.
Manages Mazzotti Reactions: In some parasitic infections, the drug can cause an inflammatory reaction as microfilariae die, which may require medical management.
Formulation Matters: Oral tablets provide systemic treatment for internal parasites, while topical applications target external infestations.

The Primary Mechanism: Targeting Parasite Nervous Systems

Ivermectin's primary anti-parasitic function is its selective targeting of glutamate-gated chloride ion channels (GluCls), which are specific to invertebrate nerve and muscle cells. These channels control the flow of chloride ions across the cell membrane, which is crucial for nerve signal transmission and muscle function. When ivermectin binds to these channels, it locks them in an 'open' state, allowing a massive influx of chloride ions.

This continuous influx of negative chloride ions causes the parasite's nerve cells to become 'hyperpolarized'—making it harder for them to fire and transmit signals. This ultimately leads to the paralysis of the parasite's pharyngeal and somatic muscles, rendering it unable to feed or reproduce. The parasite is then killed either directly by this paralysis or by the body's immune system clearing the immobilized larvae.

The Importance of Selectivity

A critical aspect of ivermectin's action is its safety margin for mammals. This selectivity is due to several key differences between the physiology of parasites and mammals.

Mammalian GluCls: Mammals do not possess glutamate-gated chloride channels in their central nervous systems (CNS). Instead, mammals use other neurotransmitter-gated channels, such as those sensitive to gamma-aminobutyric acid (GABA), which ivermectin has a lower affinity for.
The Blood-Brain Barrier (BBB): A critical protective mechanism in mammals is the blood-brain barrier, which prevents ivermectin from reaching the central nervous system in therapeutically relevant concentrations. The P-glycoprotein (P-gp) transporter, an efflux pump, is largely responsible for this, actively moving ivermectin out of the CNS.
Species Differences: In certain breeds of dogs (e.g., Collies) with a defective P-glycoprotein gene (MDR1 mutation), ivermectin can cross the BBB, leading to toxicity. This highlights the importance of the P-gp system for ivermectin's safety in most mammals.

The Pharmacokinetic Journey of Ivermectin

The way ivermectin is absorbed, distributed, metabolized, and eliminated plays a vital role in its effectiveness and safety.

Absorption: Ivermectin is absorbed into the bloodstream after oral administration. A single dose typically reaches peak plasma concentrations within 3 to 6 hours. Absorption is enhanced when the drug is taken with a high-fat meal, significantly increasing its bioavailability.
Distribution: Being a highly lipophilic (fat-soluble) drug, ivermectin distributes widely throughout the body. It tends to accumulate in fatty tissues, which serves as a reservoir for the drug. However, the blood-brain barrier effectively limits its entry into the central nervous system in most people at normal doses.
Metabolism: The liver is the primary site of ivermectin metabolism. The cytochrome P450 enzyme CYP3A4 is mainly responsible for breaking down ivermectin into several metabolites. While some metabolites retain antiparasitic activity, their elimination half-lives can be longer than the parent compound's.
Elimination: The vast majority (over 98%) of ivermectin and its metabolites are excreted in the feces via biliary secretion. Less than 1% is eliminated through urine. This process is relatively slow, contributing to its sustained antiparasitic effect. The average plasma half-life in humans is about 18 hours.

The Effect on Specific Parasitic Infections

Ivermectin is highly effective against a range of parasites, particularly those that cause tropical diseases. Its mechanism allows it to target both intestinal and skin-dwelling parasites.

Intestinal Infections

Strongyloides stercoralis: For intestinal strongyloidiasis (threadworm infection), ivermectin kills the worms living in the intestines, which helps clear the infection.

Filarial Infections

Onchocerca volvulus: In the case of onchocerciasis (river blindness), ivermectin kills the larval-stage microfilariae that cause skin and eye disease. It also temporarily sterilizes the adult female worms, preventing them from releasing more larvae for several months. Since the adult worms can live for over 10 years, repeated doses are needed to control the infection.
Wuchereria bancrofti: For lymphatic filariasis (elephantiasis), ivermectin is effective at reducing the microfilarial load in the blood.

Ectoparasitic Infections

Sarcoptes scabiei: For scabies, oral ivermectin can be highly effective by reaching the mites under the skin. A two-dose regimen is often necessary to kill newly hatched mites that emerge after the initial dose.
Lice and Rosacea: Topical formulations of ivermectin are used to treat external parasites like head lice and skin conditions like rosacea, which can be linked to Demodex mites.

Important Considerations and Adverse Effects

While generally safe at therapeutic doses, ivermectin use is not without risks, especially when misused or taken for unapproved conditions. Serious side effects can occur, particularly in individuals with high parasite loads or those who take excessive doses, such as those intended for animals.

Mazzotti Reaction: In patients with high microfilarial loads, particularly in onchocerciasis, the mass die-off of parasites can trigger a significant inflammatory response called the Mazzotti reaction. Symptoms include fever, rash, joint pain, and swollen lymph nodes.
Neurological Effects: High doses can cause ivermectin to bypass the blood-brain barrier, leading to central nervous system toxicity. This is especially risky in individuals with underlying conditions or with co-infection of Loa loa, which can increase susceptibility to encephalopathy. Overdose symptoms can include dizziness, seizures, and coma.

Oral vs. Topical Ivermectin


Feature	Oral Ivermectin (Tablets)	Topical Ivermectin (Cream/Lotion)
Absorption	Absorbed systemically into the bloodstream.	Absorbed locally through the skin, with minimal systemic absorption.
Primary Use	Intestinal parasitic worms (e.g., strongyloidiasis) and filariases (e.g., onchocerciasis).	Ectoparasites (head lice) and inflammatory skin conditions (rosacea).
Distribution	Distributed widely throughout the body, including fat tissue.	Primarily localized to the area of application on the skin.
Systemic Effect	Systemic action is required to reach internal parasites.	Acts on local skin conditions and surface-dwelling ectoparasites.
Metabolism	Metabolized primarily by the liver via CYP3A4.	Minimal metabolism occurs due to limited systemic exposure.
Risk of Overdose	Risk of central nervous system toxicity with very high doses or in compromised patients.	Very low risk of systemic toxicity due to poor absorption.

Conclusion

Ivermectin's action within the body is a sophisticated example of targeted pharmacology, exploiting a key difference in the nervous systems of parasites and mammals. By selectively activating chloride channels in parasites, it induces paralysis and death, effectively treating and controlling a range of devastating parasitic diseases. For humans, the presence of the blood-brain barrier and other physiological safeguards ensures its safety at prescribed therapeutic doses. However, misuse, overdose, or treating co-infections with high microfilarial loads can lead to serious adverse effects. This makes understanding ivermectin's specific mechanism of action critical for its safe and effective use. For further information on recommended uses, consult official health guidelines, such as those from the World Health Organization: https://www.who.int/news-room/fact-sheets/detail/ivermectin.

Frequently Asked Questions

Ivermectin kills parasitic worms by binding to their glutamate-gated chloride ion channels. This binding increases the flow of chloride ions into the parasite's nerve and muscle cells, causing paralysis and ultimately, death.

At standard therapeutic doses, ivermectin is generally safe for humans because the drug does not readily cross the blood-brain barrier, which is protected by a P-glycoprotein efflux pump. However, taking excessive doses or veterinary formulations is extremely dangerous and can cause severe toxicity, including neurological damage.

The plasma half-life of ivermectin in humans is approximately 18 hours after oral administration, though it can accumulate in fat tissue, and some metabolites have longer half-lives.

The Mazzotti reaction is an inflammatory response that can occur in patients with high microfilarial parasite loads, particularly with onchocerciasis, following ivermectin treatment. Symptoms can include itching, fever, headache, and joint pain, and are caused by the body's reaction to the dying parasites.

Certain dog breeds, like Collies, have a genetic mutation (MDR1) that affects the P-glycoprotein transporter. This allows ivermectin to enter the central nervous system, where it can cause neurological toxicity.

Yes, taking ivermectin with a high-fat meal can increase its bioavailability by about 2.5 times compared to taking it on an empty stomach.

An overdose of ivermectin can lead to serious adverse effects including nausea, vomiting, diarrhea, seizures, and coma. It is critical to seek immediate medical attention in such cases.

Despite widespread misinformation during the COVID-19 pandemic, major health organizations like the FDA and WHO do not recommend ivermectin for treating or preventing COVID-19. Studies suggesting antiviral effects were primarily in vitro and required doses far higher than those safe for human use.