Pharmacometric analyses of various ivermectin dose regimens in Kenya to inform dosing in mass drug administration trials for malaria vector control.

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Objectives A promising strategy in malaria prevention is vector control through mass drug administration (MDA) of ivermectin. A three-day ivermectin regimen (3 × 300 µg/kg) reduces mosquito survival, but campaigns may operationally struggle to achieve high coverage and adherence. Therefore, we aimed to compare the exposure of this regimen to a single dose of 400µg/kg which may be easier to implement in MDAs. Additionally, we assessed whether dried blood spot (DBS) sampling can be used in a field trial setting instead of plasma sampling.Methods Healthy adults in Kenya received either ivermectin once (1 × 400 µg/kg), or on three consecutive days (3 × 300 µg/kg). Pharmacometric analyses were conducted for both regimens using plasma and DBS.Results Trial simulations suggest that both regimens result in concentrations above the LC50 of Anopheles gambiae for 6.3-8.5 days, delivering a reasonable mosquito-killing window following ivermectin campaigns. Plasma and DBS concentrations showed a strong linear correlation (R²=0.93).Conclusion While both regimens yield comparable exposure, delivering a single 400 µg/kg dose could simplify implementation, reduce operational costs, and increase drug adherence. DBS are a viable alternative to plasma sampling in field trials.