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How do pharmacokinetics (absorption, distribution, metabolism, excretion) differ when humans ingest veterinary ivermectin formulations?
Executive summary
Human pharmacokinetics of ivermectin differ from veterinary formulations mainly because veterinary products use different vehicles, higher concentrations and routes (injectable, pour‑on, long‑acting) that change absorption rate, bioavailability, and half‑life; animal studies report slow absorption, broad distribution, low metabolism and slow excretion with half‑lives that vary by species and formulation (e.g., t1/2 up to ~8.3 days for nonaqueous injectable vehicles) [1] [2]. Reviews note formulation and route drive major PK changes and warn against extrapolating animal data to humans because species, dose and vehicle all alter exposure [3] [4].
1. Why formulation matters: vehicles, concentration and route rewrite absorption
Pharmaceutical vehicles used in veterinary ivermectin (IVM) — nonaqueous solvents, propylene glycol/glycerol formal blends, highly concentrated “long‑acting” preparations or pour‑ons — materially change how fast and how completely drug enters systemic circulation; studies show nonaqueous injectable vehicles produce a slow absorption process and markedly longer apparent biological half‑life (t1/2 ≈ 8.3 days in one report) compared with aqueous forms [2] [5]. Reviews of formulation effects emphasize that changing the vehicle or route (oral, SC/IM, topical/pour‑on) alters Cp, AUC, Cmax and bioavailability — so a veterinary product formulated to give prolonged exposure in cattle will not behave the same if swallowed or injected by a human [3] [4].
2. Distribution and persistence: broad tissue uptake and long residence in animals
Across domestic species, ivermectin shows broad distribution, slow absorption and slow excretion; biological half‑life differs by species (example order: swine 0.5 day < dogs 1.8 day < cattle ≈ sheep 2.8 day) and depends on formulation and route, producing long mean residence times and large apparent volumes of distribution in animal studies [6] [7] [1]. Long‑acting veterinary formulations intentionally raise and prolong systemic concentrations — some cattle products are concentrated (3.15%) and dosed at multiples of standard mg/kg to extend persistent antiparasitic activity [8] [5].
3. Metabolism and excretion: generally low metabolism, slow clearance in animals
Reviews summarizing animal data conclude ivermectin undergoes relatively low metabolism and slow excretion compared with many drugs; clearance and metabolite patterns vary by species and formulation, and drug residues (for example in eggs or milk) can persist after topical or injectable use in birds and livestock, underscoring prolonged systemic exposure from certain veterinary routes [1] [9]. The veterinary literature therefore flags residue and withdrawal concerns precisely because formulations alter elimination kinetics [9].
4. What this means for humans ingesting veterinary formulations
Available sources do not provide controlled human PK studies of intentionally ingesting veterinary formulations. However, the literature warns that formulation and route change PK dramatically across species and that animal data do not translate directly to humans — so swallowing or self‑injecting a veterinary parenteral or long‑acting product risks unpredictable absorption, higher or prolonged exposure, and different peak levels than approved human tablets [3] [4]. Case reports exist of clinicians using veterinary parenteral ivermectin in severe human infections, but the reviews stress limited human PK data relative to veterinary knowledge and emphasize caution [10].
5. Clinical and safety implications drawn from the reviews
Because veterinary products are formulated to deliver prolonged or higher tissue exposure (e.g., long‑acting injectables dosed at higher μg/kg), using them in humans could produce higher AUC and longer t1/2 than human‑label formulations, increasing risk of toxicity and drug residues; the reviews repeatedly state that formulation strategies are central to both efficacy and safety and that altering vehicles affects PK and therapeutic window [11] [4] [1]. Veterinary literature also links formulation to resistance management — an implicit agenda: manufacturers design veterinary formulations to maximize persistence in animals, not to meet human safety/efficacy margins [11] [8].
6. Bottom line and reporting gaps
In short, veterinary ivermectin formulations change absorption, distribution, metabolism and excretion compared with standard human formulations because of different vehicles, concentrations, dosing and routes; animal studies quantify prolonged half‑lives and high bioavailability for some veterinary products, but available sources do not present systematic human PK data after ingestion or off‑label use of veterinary formulations, so precise human risks and plasma profiles "after ingestion" are not found in current reporting [2] [1] [3] [10].