How does ivermectin distribute into tissues (including fat, brain, and lungs) and cross the blood–brain barrier in humans?
Executive summary
Ivermectin is highly lipophilic and distributes into tissues such as fat and lung, but in humans it "does not readily cross the blood–brain barrier" under normal conditions because P‑glycoprotein (encoded by MDR1/ABCB1) at the blood–brain barrier pumps the drug out; brain penetration can rise with very high doses, P‑gp dysfunction, or BBB compromise [1] [2] [3]. Available human and animal pharmacology reviews and case reports note higher tissue than plasma concentrations (including lung accumulation in some reports) but stress that central nervous system (CNS) effects are rare at therapeutic doses [4] [5] [6].
1. How ivermectin’s chemistry explains where it goes in the body
Ivermectin is a macrocyclic lactone with high lipophilicity; that chemical character drives extensive tissue distribution, especially into adipose tissue and organs with high lipid content, and contributes to detectable concentrations in tissues long after plasma levels fall [1] [4]. Reviews explicitly state ivermectin's lipophilicity explains "expensive tissue distribution" and its historical pharmacokinetic profile in humans and animals [1] [4].
2. Lung and other tissue distribution: what the literature reports
Several sources and meta-analyses note that ivermectin can accumulate in lung and other tissues at concentrations higher than plasma, and some modeling and in vitro authors have argued tissue levels may exceed in‑vitro effective concentrations in certain experimental systems [5] [4]. However, these findings are context‑dependent: experimental cell systems, modeling studies, and animal data do not directly prove clinical efficacy for indications like COVID‑19 or cancer; many clinical reviews caution against extrapolating tissue accumulation to therapeutic benefit [5] [7] [8].
3. Blood–brain barrier (BBB): the central role of P‑glycoprotein
Multiple pharmacology and toxicology reviews state ivermectin "does not readily cross the blood–brain barrier" in humans because P‑glycoprotein (P‑gp) efflux pumps at the BBB actively exclude it [2] [9] [3]. Knockout and veterinary literature show that when P‑gp is absent or nonfunctional (genetic MDR1 mutations in some dog breeds or knockout mice), brain concentrations increase dramatically and neurotoxicity follows — a mechanistic demonstration that P‑gp limits ivermectin brain entry [10] [11].
4. When ivermectin can get into the brain — documented exceptions
Case reports, toxicology briefs, and clinical summaries record that CNS penetration and encephalopathy can occur with overdose, P‑gp dysfunction, or when the BBB is compromised (for example, in severe systemic illness), and animal studies show vitamins or inhibitors of P‑gp can increase brain levels in mice [12] [13] [14]. Reviews caution that although routine therapeutic doses are generally safe neurologically, serious neurological adverse events have been reported in contexts of overdose or altered BBB/P‑gp function [2] [15].
5. Clinical safety framing and implications for human use
Longstanding clinical experience (decades of human use) supports a favorable safety profile for approved antiparasitic indications, which is commonly attributed to limited BBB penetration in people without P‑gp defects [6] [16]. Regulatory and public health authorities (e.g., FDA) emphasize ivermectin is approved for specific parasitic diseases and warn against unapproved uses; available clinical data do not support routine high‑dose or off‑label use for viral or oncologic diseases, and such practices raise the risk of toxicity if they lead to exposures high enough to overwhelm BBB exclusion [17] [7].
6. Uncertainties, competing claims, and what reporting does not show
Some meta‑analyses and advocacy sites assert lung/tissue concentrations reach levels relevant to antiviral effects and cite higher tissue accumulation [5]. Peer‑reviewed reviews, toxicology literature, and clinical commentators caution that tissue accumulation and in‑vitro activity do not equate to proven clinical benefit; available sources do not provide conclusive human data that tissue distribution produces effective antiviral or anticancer concentrations at safe doses [5] [4] [7]. In short, the mechanistic facts about distribution and BBB exclusion are well documented, but translating tissue levels into new clinical indications remains unsupported in current clinical reporting [4] [7].
7. Practical takeaways for clinicians and the public
Mechanistically, expect ivermectin to concentrate in fat and some organs (including lung) more than plasma because of lipophilicity, while being actively kept out of the CNS by P‑gp in most humans; but overdose, P‑gp defects, P‑gp inhibitors, or BBB disruption can permit brain accumulation and neurotoxicity [1] [3] [13]. Authorities warn against off‑label high‑dose use and stress that tissue distribution findings do not justify unproven therapeutic claims [17] [7].
Limitations: this summary cites pharmacology reviews, animal and human case reports, and secondary analyses from the provided search results; it does not include sources beyond those provided and therefore cannot address studies not present in this set — available sources do not mention some specific human tissue concentration time‑courses or quantitative lung:plasma ratios beyond the cited modeling and review discussions [5] [4].