What are the pharmacokinetic and toxicologic differences between human and veterinary ivermectin formulations that affect risk?
Executive summary
Human and ivermectin">veterinary ivermectin products contain the same active macrocyclic lactone but differ in concentration, formulation vehicles, and routes of administration — differences that change absorption, peak blood levels, half‑life and therefore toxicity risk [1] [2]. Clinical reports and poison‑center surveillance link ingestion or parenteral use of veterinary preparations to higher‑dose exposures and neurotoxicity in humans, underscoring that formulation and route drive most of the added danger [3] [4].
1. Formulation concentration and excipient differences drive dose disparities
Veterinary ivermectin is manufactured for animals in a wide array of forms — high‑concentration injectables, pour‑on/topical solutions, and oral pastes — often at concentrations and total doses intended for large livestock rather than per‑kilogram human dosing; human products are oral tablets or topical creams formulated for controlled, lower dosing [2] [5]. Because many veterinary preparations are intended to deliver milligrams per kilogram to animals weighing hundreds of kilograms, a single veterinary dose or a small mismeasured amount can deliver vastly higher absolute ivermectin exposure to a person than a human tablet provides [2] [6].
2. Vehicles and route of administration alter pharmacokinetics and exposure
Formulation vehicles (aqueous vs nonaqueous solvents, ethanol‑based liquids, emulsions) strongly affect absorption rate, bioavailability, and apparent half‑life; nonaqueous injectable vehicles used in veterinary controlled‑release products produce much slower absorption and markedly prolonged apparent biological half‑lives compared with simple oral tablets [7] [2]. In humans, oral ivermectin is absorbed rapidly (absorption half‑life ~0.5–2.5 hours) and has been characterized with Cmax and terminal t½ in clinical studies, whereas veterinary routes (subcutaneous, intramuscular, pour‑on) and nonaqueous carriers yield different Cmax, AUC and prolonged systemic exposure in the target species [8] [1] [9].
3. Species differences complicate direct extrapolation of veterinary PK to humans
Pharmacokinetic parameters vary markedly by species — for example, reported biological half‑lives differ across swine, dogs, cattle and sheep — meaning veterinary PK data reflect animal physiology and vehicle choices more than human behavior of the drug [9] [10]. Translating a veterinary product’s dose and kinetics to a human is therefore unreliable: same product applied to an animal may give a therapeutic exposure in that species but unpredictable and potentially toxic plasma levels in a person because absorption, distribution, metabolism and elimination differ [1] [10].
4. Clinical toxicology: higher doses, parenteral use, and documented harms
Poison‑center and clinical series during the COVID‑19 period document that people who used veterinary ivermectin tended to ingest much larger cumulative doses and were more likely to be hospitalized; in one case an intravenous veterinary ivermectin bolus given after high oral dosing produced severe neurotoxicity with measured plasma ivermectin ~188 ng/mL and neurologic deterioration, implicating route and dose in harm [3] [4]. Case series emphasize that neurotoxicity (confusion, ataxia, seizures) occurs at supratherapeutic exposures and that intravenous administration of veterinary formulations is particularly dangerous and not authorized in humans [4] [3].
5. Practical risk modifiers and monitoring limitations
Risk increases with higher per‑kg dose, use of non‑tablet formulations or parenteral routes, and co‑factors that alter absorption or clearance (e.g., ethanol‑based formulations that increase bioavailability, impaired gut motility with parasitic ileus, or drug interactions affecting metabolism) — yet the human pharmacokinetic literature remains relatively sparse compared with veterinary data, limiting precise risk prediction [8] [11]. Regulatory and clinical authorities therefore warn against using veterinary products in humans because differences in concentration, excipients and intended route translate into unquantified and demonstrable safety hazards [5] [3].
6. Bottom line and data gaps
The active molecule is shared across human and animal products, but formulation (vehicle, concentration), route (oral tablet versus injectable/pour‑on), and species‑specific pharmacokinetics create substantial differences in absorption, peak concentrations and half‑life that materially increase toxicity risk when veterinary products are used in people; case reports and poison‑center data substantiate that these differences have produced harm [2] [7] [3] [4]. Remaining gaps include precise human pharmacokinetics after accidental exposure to specific veterinary vehicles and quantification of toxicity thresholds by formulation, information that the reviewed human literature describes as limited compared with extensive veterinary studies [11] [1].