How do pharmacokinetics of ivermectin differ between horses and humans?
Executive summary
Ivermectin’s pharmacokinetics differ by species: typical therapeutic oral doses (≈150–200 µg/kg) produce peak plasma concentrations (Cmax) in the low tens of ng/ml across species, but absorption rate (Tmax), Cmax and half‑life vary by animal and formulation — in horses oral ivermectin 0.2 mg/kg produced Cmax ranges ~6–43 ng/ml and Tmax from 2–36 hours depending on season and study [1] [2] [3]. Human single doses (commonly 150 µg/kg) show different plasma time‑courses (e.g., enterohepatic recycling with secondary rises 6–12 h post‑dose) and generally similar-order Cmax values reported in reviews, but species‑specific distribution, metabolism and routes of administration drive the key differences [4] [3].
1. Species matters: broad summary of how kinetics shift between horses and people
Ivermectin pharmacokinetics are explicitly species‑dependent: reviews and comparative studies state that absorption, distribution, metabolism and excretion differ across hosts, so parameters measured in horses cannot be applied directly to humans [5] [3]. Veterinary literature documents oral, pour‑on and subcutaneous routes in equids with variable bioavailability and Tmax; human reviews describe mostly single oral doses with different plasma profiles including possible enterohepatic recycling [3] [4].
2. Peak levels (Cmax) — similar magnitude but variable ranges
Textbook and review sources report that therapeutic doses (150–200 µg/kg) produce Cmax values in the same order of magnitude (low tens of ng/ml) across domestic species and humans: cited ranges include roughly 11–54 ng/ml across animals and similar low‑ng/ml concentrations noted for humans in pharmacokinetic studies [3]. Specific horse studies reported individual horse Cmax values spanning ~6.4–43.1 ng/ml depending on season and formulation [1] [2].
3. Time to peak (Tmax) — slower and more variable in horses
Equine studies show Tmax can be prolonged and variable: one horse study found Tmax averaged ~9.8 h in spring but slowed to ~21.9 h in autumn, with individual Tmax from 2 to 36 h depending on season and animals [1]. Human studies frequently document an initial decline after dosing followed by a secondary plasma rise 6–12 h later, consistent with enterohepatic recycling rather than the broad seasonal variability seen in equine field studies [4].
4. Distribution and elimination — broader tissue distribution and slow elimination in animals
Reviews emphasize that ivermectin displays broad distribution, low metabolic clearance and slow excretion in domestic animals; kinetics vary with route, formulation, breed and physiological status [3]. Horse and other large‑animal data show slow absorption and prolonged presence in plasma and tissues. Human mini‑reviews report relatively low metabolism and long persistence too, but the patterns of tissue distribution and clearance depend on species‑specific physiology [3] [4].
5. Formulation, route and physiology drive differences — not just species
Both human and veterinary sources underline that formulation (paste, liquid, pour‑on, subcutaneous) and route materially affect bioavailability, Tmax and Cmax: horse studies compare liquid nasogastric vs paste, and pour‑on or injection produces distinct profiles [5] [2] [3]. Breed, body condition and season altered horse kinetics in the cited trials [2] [1]. Human reports note food and drug interactions are under‑studied but can influence absorption and interactions [4].
6. Safety, dosing context and practical implications
Therapeutic human dosing is typically 150 µg/kg (single dose) and veterinary equine dosing commonly 200 µg/kg oral paste; both produce low‑ng/ml plasma concentrations with a wide safety margin noted in reviews [3] [4]. Regulatory and product labels emphasize species distinctions — for example, equine ivermectin paste labels warn “Do not use in horses intended for human consumption” and instruct veterinary oversight, underscoring that veterinary formulations and dosing are not interchangeable with human therapy [6].
7. Limits of available reporting and open questions
Available sources summarize general trends and give numerical ranges, but direct side‑by‑side head‑to‑head human vs horse pharmacokinetic trials using identical formulations and analytical methods are not supplied in this set of documents; therefore precise comparative metrics (e.g., mean half‑life differences under identical conditions) are not found in current reporting [5] [3]. Also, food effects and many drug–drug interactions in humans remain under‑reported in the cited mini‑review [4].
Bottom line: horses and humans attain broadly similar low‑ng/ml ivermectin plasma concentrations after standard therapeutic doses, but horses show larger variability in Tmax/Cmax depending on formulation, season and breed; distribution and elimination are species‑specific and formulation‑dependent, so veterinary data cannot be used to guide human dosing [1] [2] [3] [4] [5].