How do excipients like polyvinylpyrrolidone and arabinogalactan affect the pharmacokinetics of ivermectin in horses?
Executive summary
Polyvinylpyrrolidone (PVP) and arabinogalactan (AG) act as formulation excipients that increase ivermectin’s apparent solubility and modify absorption, and mechanochemical complexes containing these excipients have produced greater anthelmintic efficacy at lower doses in some livestock studies [1] [2]. The pharmacokinetic consequences in horses are plausible and consistent with established formulation effects on ivermectin—altered Tmax, Cmax, and persistence—but direct, large-scale horse pharmacokinetic data specifically dissecting PVP or AG effects are limited to small or preliminary studies [3] [4] [1].
1. Ivermectin pharmacokinetics in horses: a formulation-sensitive baseline
Ivermectin displays slow absorption, broad tissue distribution, low metabolism and slow excretion, and those kinetic traits vary with species, route and formulation—making formulation effects especially important in horses where oral pastes are common [4] [3] [5]. Prior work documents that formulation and administration route change Tmax, Cmax, half-life and bioavailability across species and in horses specifically, so any excipient that changes solubility or release can meaningfully reshape plasma exposure [6] [5] [7].
2. What polyvinylpyrrolidone (PVP) does to ivermectin formulations
PVP is used to improve drug solubility and to create solid dispersions or solvent vehicles that enhance dissolution; it has been included at 5% in a solvent mix to aid ivermectin administration in goat pharmacokinetic studies, demonstrating its practical role in formulation vehicles [8]. Reviews of ivermectin formulation work show that solvent composition and solubility enhancers regulate absorption rate and bioavailability—so PVP’s solubilizing role plausibly increases oral absorption or speeds initial uptake when incorporated into an ivermectin paste or solvent [3] [5].
3. What arabinogalactan (AG) does and the supramolecular complex data
Arabinogalactan, a polysaccharide, has been used to form solid dispersions and supramolecular complexes with ivermectin that increase the apparent solubility of the active ingredient; mechanochemical modification with AG produced improved solubility metrics in study tables and was central to formulations tested in horses and sheep [2] [1]. In sheep, AG-conjugated ivermectin formulations were reported to be 5–10 times more effective than standard doses in reducing helminth egg counts, implying substantially altered pharmacodynamic exposure attributable to formulation [1].
4. Direct horse evidence: efficacy signals, limited PK resolution
A Russian study that prepared antiparasitic pastes using joint mechanochemical treatment of ivermectin with PVP and AG reported maintenance of clinical parameters and significant reductions in parasite egg counts in treated horses, and noted that a threefold lower dose retained activity (151 horses in broader evaluation for activity; other equine ivermectin work remains small—most horse PK studies are older and limited) [1] [2]. However, those equine reports focus on efficacy and solubility metrics rather than detailed plasma PK parameters (Tmax, Cmax, AUC) specifically attributed to PVP or AG in large, controlled pharmacokinetic studies in horses [1] [2].
5. Mechanistic interpretation: solubility → absorption → exposure
Mechanistically, excipients that increase ivermectin solubility or form supramolecular complexes can increase the fraction absorbed and/or alter the rate of absorption, which translates into higher or faster Cmax, shorter Tmax, and potentially larger AUC—effects documented broadly for ivermectin when formulation or solvent composition is changed [6] [7]. For subcutaneous products, solvent polarity alters release from the depot and extends apparent half‑life; for oral horse pastes, PVP/AG-driven solubility increases plausibly shift oral bioavailability and thereby improve efficacy at lower doses as seen in sheep and preliminary equine work [5] [1].
6. Caveats, competing views and possible incentives
The evidence for PVP and AG improving ivermectin PK and efficacy is strongest for in vitro solubility gains and in vivo efficacy signals in small studies or other species (sheep, goats), while rigorous, large-scale horse pharmacokinetic trials isolating excipient effects on plasma PK parameters are sparse—reviews caution that species, route, body condition and formulation all interact, so extrapolation is uncertain [2] [4] [3]. Commercial or academic interest in proprietary formulations can bias emphasis on efficacy gains without publishing full PK datasets, so independent pharmacokinetic validation in horses remains necessary to confirm dose-reduction claims [1] [7].
7. Practical takeaway for equine therapeutics and research needs
The balance of mechanistic rationale and preliminary data indicates PVP and AG can and do change ivermectin’s pharmacokinetic behavior by improving solubility and absorption, which has translated into enhanced anthelmintic activity at lower doses in some studies, but definitive horse-specific PK parameters (Cmax, Tmax, AUC, half‑life) tied solely to these excipients need larger controlled studies for confirmation before changing dosing recommendations [1] [3] [4].