Understanding Toxicokinetics: Ivermectin and Its Dose Thresholds
In the world of pharmacology, toxicokinetics is a vital area of study that helps us understand how substances interact with the body, especially regarding their safety and potential toxicity. When it comes to ivermectin, a widely recognized antiparasitic drug, its safety thresholds and potential repurposing in cancer care make it an important topic. Let’s break down the science.
Learn even more about Ivermectin.
What Is Toxicokinetics?
Toxicokinetics focuses on how a substance is absorbed, distributed, metabolized, and excreted by the body—essentially tracking its journey and effects at different doses. A critical metric in this field is the Lethal Dose 50 (LD50).
LD50: This refers to the dose of a substance that causes death in 50% of a group of test subjects (usually animals) during experiments. It's a standard way to measure toxicity.
Understanding the LD50 helps researchers determine safe and effective doses for humans when translating findings from animal studies.
How Is LD50 Tested Across Species?
Different species metabolize substances differently, so LD50 varies depending on the animal tested. Here’s a breakdown:
Mice:
Oral LD50: 25 mg per kilogram (mg/kg) of body weight.
Human Equivalent Dose (HED): Translating this to humans using a standard formula gives us approximately:
182 mg for a 200-pound man.
155 mg for a 171-pound woman.
Intraperitoneal (I.P.) LD50: 30 mg/kg (HED: ~220 mg for males, ~189 mg for females).
Rats:
Oral LD50: 50 mg/kg (HED: ~8.01 mg/kg).
I.P. LD50: 55 mg/kg (HED: ~8.91 mg/kg).
Other Animals:
Rabbits (Topical Application): LD50 is 406 mg/kg.
Dogs (Oral Administration): LD50 is 80 mg/kg (HED: ~43.24 mg/kg).
Monkeys (Oral Administration): LD50 is 200 mg/kg.
Key Takeaway: The higher up an animal is on the evolutionary scale, the less toxic ivermectin tends to be. For example, it’s far less toxic to monkeys (and by extension, humans) than to mice.
Human Toxicity Data
A 1999 study reviewed 19 cases of avermectin poisoning (a class of drugs that includes ivermectin) reported to poison centers. Here’s what it found:
Mild or No Symptoms:
12 patients ingested an average of 23 mg/kg or were exposed through skin or inhalation. Symptoms were minimal or nonexistent.
Severe Symptoms:
7 patients experienced significant toxicity, including:
Coma: 7 cases.
Aspiration with Respiratory Failure: 4 cases.
Hypotension (Low Blood Pressure): 3 cases.
These severe cases were associated with much higher doses—an average ingestion of 100.7 mg/kg.
For humans:
A 200-pound man would need to ingest approximately 1400 mg of ivermectin to reach dangerous levels.
A 171-pound woman would need approximately 1197 mg.
Why Does This Matter for Cancer Research?
Repurposed Medications
Ivermectin’s potential use in oncology is a promising area of research. Its mechanisms include:
Inhibiting Cancer Cell Signaling: Ivermectin disrupts pathways cancer cells rely on for growth and survival.
Reducing Cancer Cell Proliferation: It slows the spread of cancer cells.
Modulating the Immune Response: By enhancing the body’s ability to detect and fight cancer, ivermectin shows potential as part of an integrative cancer care approach.
However, understanding its toxicokinetics ensures that therapeutic doses remain far below harmful levels, ensuring patient safety.
Definitions
Absorption: How a drug enters the bloodstream after being taken.
Distribution: How the drug spreads throughout the body to different tissues and organs.
Metabolism: How the body breaks down the drug, usually in the liver.
Excretion: How the drug and its metabolites are removed from the body, often through urine or feces.
Intraperitoneal (I.P.): A method of delivering a substance directly into the abdominal cavity, used in animal studies.
Lethal Dose 50 (LD50): The dose of a substance that causes death in 50% of test subjects during studies.
Human Equivalent Dose (HED): A formula used to calculate a safe dose for humans based on animal data.
Supporting Evidence
Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–61. doi: 10.1096/fj.07-9574LSF.
Chung K, Yang CC, Wu ML, Deng JF, Tsai WJ. Agricultural avermectins: an uncommon but potentially fatal cause of pesticide poisoning. Ann Emerg Med. 1999;34:51–7. doi: 10.1016/s0196-0644(99)70271-4.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
Conclusion
Understanding the toxicokinetics of ivermectin provides a foundation for its safe and effective use in innovative therapies like cancer treatment. By ensuring doses stay well within safe limits, ivermectin can be explored further as a repurposed medication with the potential to save lives.
For more insights on integrative cancer care, visit Pre-Scribed.com.