What are measured ivermectin concentrations in human lung tissue after repeated oral dosing?

1. Why the data gap exists: lung tissue in humans has not been measured

Multiple reviews and modeling papers state explicitly that ivermectin concentrations in human lung tissue have not been measured, forcing reliance on animal tissue data (calf, goat, pig) and modeling to predict human lung exposure ^{[4] [3] [5]}; authors warn this is a hard limitation for translating in vitro SARS‑CoV‑2 inhibition to clinical dosing because tissue penetration, protein binding in lung, and transporter effects are uncertain ^{[4] [5]}.

2. What animal measurements show and how they are used to infer human lungs

Tissue studies in calves and other animals found lung ivermectin concentrations higher than plasma but far below the 5 μM antiviral concentration used in early cell culture work: calf lungs after a 200 μg/kg injection reached ~100 ng/g (~0.1 μM) ^{[6] [5]}, and some animal distributions report lung:plasma ratios of roughly 2–3× depending on species and route ^{[4] [7]}. These animal lung values are routinely multiplied by human plasma Cmax in simulations to predict human lung Cmax because direct human lung biopsies are lacking ^{[1] [2]}.

3. Modelled human lung concentrations after oral dosing — central estimates

mPBPK and population PK simulations using human plasma data plus animal lung:plasma coefficients predict that an approved oral dose (200 μg/kg) would produce a lung Cmax far below the in vitro IC50; Schmith et al. report a predicted lung concentration of ~0.0873 μM for the approved dose and ~0.820 μM after a 10× oral dose, both beneath the 2 μM IC50 reported in some studies ^{[1] [8]}. Jermain et al.’s mPBPK simulations similarly show median lung concentrations well below the published in vitro IC50 (~1750 ng/mL) after single oral doses including up to 120 mg, with confidence intervals demonstrating large shortfalls versus antiviral thresholds ^[2]. A slide summary estimated a peak lung concentration ~772 ng/mL using a 120 mg dose in some models, still short of the 5 μM antiviral benchmark used by Caly et al. ^{[9] [2]}.

4. Conflicting findings and higher estimates from clinical/experimental work

Not every analysis concludes ivermectin lung exposure is negligible: an open randomized trial of high‑dose oral ivermectin reported plasma PK and viral kinetics that led its authors to estimate median lung levels >395 ng/g, arguing a concentration–response relationship with viral decay and tolerability of higher doses in a limited cohort ^[10]. Reviewers caution that such extrapolations — and the trial’s estimated lung values — rest on assumptions about distribution equivalence between species and about how lung homogenate concentrations relate to active concentrations at the epithelial surface ^{[5] [3]}.

5. Routes and doses that reach lung antiviral concentrations in animals

Direct pulmonary delivery (nebulized or inhaled formulations) and intratracheal dosing in animal models achieve lung and bronchoalveolar lavage fluid concentrations above in vitro antiviral thresholds for hours to days, and inhalational approaches are proposed to overcome oral bioavailability and first‑pass limits; however, inhaled ivermectin requires preclinical safety and human dose‑finding because lung and systemic toxicity risks differ from oral dosing ^{[11] [12] [3]}.

6. Bottom line and reporting caveats

Measured human lung concentrations after repeated oral ivermectin are not available in the literature; all numerical "lung" values for humans derive from animal tissue measurements scaled by plasma PK or from PBPK simulations, which generally predict lung levels below the in vitro antiviral IC50 at approved oral doses and even at many higher oral doses, though a minority of clinical extrapolations suggest higher possible lung burdens — each approach carries assumptions and limitations explicitly acknowledged by the cited authors ^{[4] [1] [2] [10]}.