What are typical plasma half-life ranges of oral ivermectin in adults and factors that alter it?
Executive summary
Published measurements of the plasma elimination half‑life of oral ivermectin in adults vary widely, with regulatory labels and some clinical studies reporting about 18 hours while other pharmacokinetic trials and population analyses report values from roughly 12 hours up to multiple days (12–91 hours in the sources provided) [1][2][3][4]. This spread reflects real biological factors—high lipophilicity and protein binding, variable bioavailability with food or alcohol, metabolism by hepatic CYP enzymes—and important differences in study methods and sampling [3][5][6][2][7].
1. Typical reported half‑life ranges — what the sources say
Official prescribing information for human oral ivermectin (Stromectol) states a plasma half‑life of approximately 18 hours following oral administration [1][8][5][9], while clinical pharmacology reviews and PK studies cite wider ranges: some reviews and trials report half‑lives from about 12 to 66 hours (commonly cited range) [2][10], a PLOS Neglected Tropical Diseases study recorded half‑lives in certain groups of 81–91 hours when measuring up to 168 hours post‑dose [2], and other literature frames the elimination as on the order of 1–3 days (≈24–72 hours) or reports specific single‑study estimates such as ~36 hours [3][4]. Population pharmacokinetic analyses also produce somewhat different summary parameters depending on data and modelling choices [11][12].
2. Why reported values diverge — biological distribution and study design
Ivermectin’s pharmacokinetic profile combines rapid absorption with extensive tissue distribution because the drug is highly lipophilic and >90% protein‑bound, producing deep peripheral compartments that can prolong apparent terminal elimination depending on sampling duration and assay sensitivity [3]. Different studies use variable dose levels, fed versus fasted conditions, sampling windows (some measure only a few days, others up to 168 hours), and analytical methods (e.g., HPLC), all of which change calculated half‑life estimates; population PK modelling choices (compartmental structure, handling of sparse samples) further shift reported elimination half‑lives [2][10][11][12].
3. Key factors that alter ivermectin half‑life in adults
Food substantially increases oral bioavailability—administration with a high‑fat meal has been shown to raise systemic availability by roughly 2.5‑fold versus fasting administration, which affects plasma concentrations and may change apparent elimination metrics [5][1]. Alcohol co‑ingestion has been shown to raise plasma levels in at least one volunteer study (beer versus water), and co‑use is discouraged because of central nervous system interactions with GABAergic pathways as well as altered kinetics [6]. Hepatic metabolism—primarily via CYP3A4 with minor contributions from other CYPs—determines clearance, so enzyme activity (drug interactions, genetic variability, liver function) can change half‑life [2][7]. Total body weight influenced clearance and central volume in population analyses, although surprisingly body fat markers were not always predictive despite ivermectin’s lipophilicity; other physiological states (age, organ function) were not consistently characterized across studies [11][12]. Enterohepatic circulation was evaluated and did not appear to meaningfully influence PK in one population study of healthy volunteers, but tissue sequestration can prolong low‑level persistence that may be detected with long sampling [12][3].
4. Practical interpretation and limits of the evidence
For clinical and regulatory use the conservative summary of “approximately 18–20 hours” appears in drug labels (reflecting certain controlled studies), but a fuller view from the literature supports a broader plausible terminal half‑life (roughly 12 hours up to several days or longer in specific measurements), meaning reported half‑life depends on dose, food/alcohol status, assay windows and modelling choices [1][2][3][5]. The evidence base is imperfect: relatively few comprehensive PK studies exist, assays and sampling durations vary, and population variability (enzyme function, co‑medications, disease states) remains incompletely characterized in adults, so reported ranges should be interpreted as context‑dependent rather than a single immutable value [2][11][12]. Where precise dosing or interaction decisions matter, refer to product labeling and consult pharmacology specialists because the literature documents both short and much longer apparent elimination phases depending on how and when ivermectin is measured [5][2].