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What are ivermectin’s pharmacokinetics and elimination half-life in humans?
Executive summary
Ivermectin is absorbed orally (only approved systemic route in humans), shows multi-compartment kinetics with peak plasma concentrations a few hours after dosing, large volume of distribution, and elimination half-lives reported variably depending on formulation and model — typically on the order of ~12–66 hours in humans in published studies and reviews (mini-review, population PK and clinical studies) [1] [2] [3]. Higher-dose and formulation studies show altered exposure (Cmax/AUC) but generally similar elimination patterns across studies [4] [5].
1. How ivermectin gets into and moves through the body — basic PK picture
Clinical reviews and pharmacokinetic papers describe ivermectin after oral dosing as being characterized by either one- or two‑compartment models; absorption leads to measurable plasma concentrations within hours, and the drug distributes widely with a relatively large apparent volume of distribution — this is the consensus summarized in the mini‑review and malaria‑focused pharmacologic reviews [1] [2]. Population PK analyses for fixed‑dose combinations also modeled ivermectin with two compartments and found that clearance and volume scale with body weight [6].
2. Absorption and peak concentrations: timing and formulation matters
Oral administration is the approved systemic route and studies document that Cmax and AUC vary with formulation (tablets/capsules vs. oral solution) and with fed vs. fasted states; an oral solution can increase systemic exposure relative to solid oral forms [1] [5]. In clinical dose‑escalation work and population PK studies, peak plasma levels typically occur within a few hours after dosing (reports summarized in [4]; [1]1).
3. Elimination half‑life: why you see a range of values in the literature
Published human studies and reviews report a range of elimination half‑lives depending on dose, analytic method and compartmental model; the mini‑review and subsequent human PK studies indicate half‑lives that can span from roughly half a day to multiple days depending on the parameter estimated and the study design [1] [2]. Dose‑escalation clinical trials and population PK work used model‑dependent methods (one‑ vs two‑compartment) which produces differing terminal half‑life estimates; those sources document variability rather than a single uniform t1/2 [4] [3].
4. Metabolism and excretion: role of CYP3A and metabolites
Ivermectin is metabolized in humans, with CYP3A4/5 implicated in producing multiple metabolites; recent human volunteer metabolite work isolated nine metabolites after a 12 mg dose and tracked their kinetics over days to understand both parent‑drug and metabolite profiles [7]. Reviews and PK papers note interactions with transporters (ABCG2/MDR1) and that metabolism/excretion patterns (and therefore systemic persistence) are influenced by these pathways [8] [7].
5. High‑dose studies and special formulations — safety and PK changes
Controlled escalation trials administering up to 120 mg single doses (and repeated regimens) showed ivermectin was generally tolerated and documented plasma concentration–time profiles across doses; such studies confirm exposure increases with dose but report elimination behavior broadly consistent with lower‑dose studies, again subject to modeling choice [4] [9]. A fixed‑dose 18 mg formulation PK study similarly characterized exposure and supported modeling for children and adults [3].
6. Implications for efficacy, dosing and off‑label use debates
Sources emphasize ivermectin’s well‑established antiparasitic uses and its safety margin at approved dosing; however, they also note that pharmacokinetic variability (formulation, dose, weight, transporter/genetic differences) complicates extrapolations when considering non‑approved uses [2] [3]. Drug compendia caution against unproven indications without high‑quality clinical data and highlight that PK alone does not establish efficacy for other diseases [8].
7. Limits of the available reporting and what’s not shown
Available sources compile many human PK studies and reviews but do not present a single consensus numeric half‑life applicable to every clinical scenario; instead they show a range and emphasize model dependence, formulation effects and subject variability [1] [2] [4]. Specific claims about an exact universal t1/2 or precise dosing for unapproved indications are not supported in the cited literature [1] [4] [3].
If you want, I can extract the specific half‑life estimates and key PK parameters reported in individual human studies (e.g., mean t1/2, Cmax, Tmax, AUC per study) from these sources and tabulate them with dosing and model used.