How do absorption and bioavailability differ for oral versus topical versus injectable ivermectin in humans?
Executive summary
Oral ivermectin is the standard human route and produces moderate systemic bioavailability that is sensitive to formulation and food (notably high-fat meals) and to intestinal metabolism and efflux mechanisms [1] [2] [3]. Topical ivermectin yields very limited transdermal absorption and markedly lower systemic concentrations than oral dosing [4] [5]. Parenteral/subcutaneous injections (used widely in veterinary medicine and reported in some human rescue cases) give the highest and most sustained systemic exposure and are generally more bioavailable than oral or topical routes [6] [7] [8].
1. Oral: moderately well absorbed but formulation- and context-dependent
Oral ivermectin is described across multiple reviews and clinical reports as “moderately well absorbed,” with an absorption half-life on the order of roughly 0.5–2.5 hours and an oral terminal half-life around 15–20 hours in adults after standard doses [2] [5] [8]. Systemic exposure (AUC and Cmax) varies substantially by formulation: ethanol-based oral solutions show roughly twofold higher bioavailability than solid tablets or capsules in head-to-head studies [6] [9] [8]. Food—especially high‑fat meals—can further increase oral bioavailability; a labeled formulation showed an approximate 2.5-fold increase in exposure when dosed with a high‑fat meal [3]. Finally, presystemic loss through intestinal CYP3A4 metabolism and P‑glycoprotein efflux reduces net absorption and creates interindividual variability and drug–drug interaction potential [2] [10].
2. Topical: local effect with minimal systemic uptake
Topical ivermectin formulations (creams and lotions for rosacea, head lice, scabies) are designed for local effect and produce very low systemic levels compared with oral dosing; mean Cmax after repeated topical use was measured in the low single‑digit ng/mL range versus tens of ng/mL after a 12 mg oral dose [5]. Multiple clinical pharmacokinetic studies and reviews state there is little transdermal absorption after topical application and that repeated topical use reaches low steady‑state systemic exposures, indicating absorption through intact human skin is limited [4] [5]. Animal and in vitro data show some dermal uptake is possible but human clinical data consistently report far lower systemic bioavailability from topical routes than from oral or parenteral administration [8] [5].
3. Injectable/subcutaneous: superior bioavailability and prolonged exposure
Subcutaneous or intramuscular injections—common in veterinary practice and used in select human clinical salvage cases—produce much higher systemic concentrations and more sustained exposure than oral dosing, with slower absorption and longer apparent persistence at therapeutic levels [6] [7] [8]. Case reports in severe disseminated strongyloidiasis document low plasma levels after oral therapy followed by marked increases (for example, from ~1.1 ng/mL after extensive oral dosing to 7.9 ng/mL after subcutaneous dosing) and evidence of prolonged antiparasitic effect [6]. Reviews summarizing animal and human data conclude parenteral routes are generally the most efficient for achieving systemic ivermectin levels and that formulation (vehicle) strongly influences absorption kinetics from the injection site [7].
4. Clinical implications, variability, and gaps
These route-dependent differences have practical consequences: oral dosing is convenient but yields variable systemic exposure dependent on formulation, food, intestinal metabolism, and P‑gp activity; topical therapy minimizes systemic exposure and is appropriate when a local effect suffices; injectable forms achieve higher, longer systemic exposure but are not widely approved for humans and carry formulation- and safety‑driven considerations [9] [3] [7]. The reviewed literature also flags important gaps and qualifications: most human approvals and safety data apply to oral and topical products, not to injected veterinary formulations, and variability between brands and vehicles can be large [7] [11]. Where assertions fall outside the provided sources—for example, broad safety profiles of novel injectable human formulations—reporting is limited and should be treated as evolving [12] [13].
5. Competing perspectives and hidden agendas in reporting
Some industry and developmental reports emphasize improved bioavailability of novel oral or parenteral formulations as a competitive advantage, while regulatory labels and clinical reviews emphasize established oral dosing and topical use with well‑characterized safety profiles; these differing emphases reflect commercial incentives to promote new formulations and conservative regulatory caution about off‑label injectable use in humans [12] [3] [13]. Independent pharmacokinetic studies and regulatory labels remain the most reliable sources for comparing systemic exposure across routes; where only animal or preliminary proprietary data exist, conclusions about human injectable use should be cautious [7] [8].