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What are the typical human dosing regimens of ivermectin and how do they affect plasma concentrations?
Executive summary
Typical human ivermectin regimens for approved parasitic indications are single oral weight‑based doses around 150–200 µg/kg (often quoted as 0.15–0.2 mg/kg), with repeat dosing used for some conditions (e.g., scabies, mass‑drug administration) and higher or multi‑day regimens tested experimentally for malaria control or severe infestations (e.g., 600 µg/kg/day ×3) [1] [2] [3] [4]. After a standard single oral dose (for example a 12 mg tablet representing ~165 µg/kg in trials), peak plasma concentrations (Cmax) occur ~4 hours post‑dose and typical Cmax values reported are roughly 30–50 ng/mL for therapeutic 150–200 µg/kg doses, with bioavailability rising when taken with food (especially high‑fat meals) and metabolites persisting longer than the parent drug [5] [6] [7] [8].
1. What clinicians typically prescribe: single, weight‑based doses for parasitic infections
For routine human use, ivermectin is usually given as a single oral weight‑based dose: many clinical references list 150–200 µg/kg (0.15–0.2 mg/kg) as the standard therapeutic range for onchocerciasis, strongyloidiasis and similar parasitic infections, with repeat dosing schedules (e.g., repeat after 7–14 days for scabies) or annual mass administration strategies (e.g., 0.4 mg/kg once yearly in some filariasis programs) used where indicated [1] [2] [9] [10]. Mass drug administration (MDA) protocols commonly use single‑dose approaches but may vary by program [3].
2. Alternative regimens evaluated in trials and field work
Investigators have tested higher or multi‑day regimens for specific goals. For malaria transmission reduction, modeling and trials have explored single high doses (e.g., 800 µg/kg) or multi‑day regimens such as 600 µg/kg/day for 3 days to extend the time blood levels exceed mosquito‑lethal thresholds; simulations showed the 600 µg/kg ×3 regimen produced similar Cmax to a single 800 µg/kg dose while prolonging time above LC50 [4]. For severe crusted scabies or refractory infestations, dermatology literature and CDC‑referenced approaches describe multi‑dose schedules (e.g., several doses on days 1,2,8 or 1–5,8–15 depending on severity) [10].
3. How dosing maps to plasma concentrations (Cmax, Tmax, half‑life)
Pharmacokinetic studies show dose‑proportional plasma concentrations and a Tmax for the parent drug around 4 hours after oral dosing; a commonly cited example is two studies of single 12 mg doses (mean ~165 µg/kg) yielding mean peak plasma concentrations of the major component in the 30–47 ng/mL range (ranges in volunteers spanned ~13.9–101.1 ng/mL) [5] [11]. Reviews and PK texts report Cmax ≈38–46 µg/L (equivalent to ng/mL) after 150–200 µg/kg and note intestinal absorption is increased roughly twofold with food (high‑fat meals) and altered by beverages like beer [6] [12] [7]. The parent drug’s terminal half‑life is commonly reported near 18–20 hours, while metabolites have longer half‑lives (metabolite peaks may occur later, ~7 h, and their elimination may be ~72 h), which can extend pharmacologic presence beyond the parent compound [5] [8].
4. Clinical and practical caveats that affect plasma levels
Plasma concentrations vary considerably between individuals: factors include dose, feeding state (food increases bioavailability), body composition and BMI (lipophilicity and adipose distribution alter volume of distribution), protein binding (>90%), and possibly enterohepatic recycling [6] [13] [8]. Dried blood spots correlate well with plasma but tend to read ~30% lower, a practical note for field pharmacokinetic work [13]. Package inserts and trials report wide intersubject ranges of Cmax even for the same mg/kg dose [5] [11].
5. Where sources disagree or are limited
Clinical dosing guidance is broadly concordant around 150–200 µg/kg for single‑dose therapy, but dosing recommendations diverge by indication (single vs repeat vs annual MDA) and experimental malaria work examines much higher regimens; sources present modeled or trialed higher doses but not universal clinical adoption [2] [4] [3]. Sources consistently report dose‑proportional plasma levels and food effects, but precise Cmax and half‑life ranges differ across studies and depend on analytical methods and participant characteristics [5] [6] [14].
6. Takeaway for clinicians and researchers
Standard human practice: weight‑based single doses ~150–200 µg/kg are the norm for approved parasitic uses; Cmax after such dosing is on the order of tens of ng/mL with Tmax ≈4 h and a parent‑drug half‑life ~18–20 h, while metabolites and tissue partitioning can extend bioactivity beyond those numbers [1] [5] [8]. For nonstandard objectives (e.g., malaria vector control), higher or multi‑day regimens have been modeled and trialed to raise and prolong plasma exposure, but those regimens are investigational and context‑specific [4]. Available sources do not mention routine use of ivermectin for COVID‑19 as an approved regimen [15] [16].