Information from the abstract
Abstract Ivermectin is used in the treatment of several neglected tropical diseases. Studies have shown that it effectively kills anopheline mosquitoes. However, the relationship between the pharmacokinetic properties and mosquito-lethal effects have not been described quantitatively. Pharmacokinetic properties and mosquito-lethal effects associated with a single oral administration of ivermectin were evaluated in two healthy volunteer trials in Thailand. All data were pooled and analysed using nonlinear mixed-effect modelling. Ivermectin and metabolites were described by a parent-metabolite model. When co-administered with dihydroartemisinin-piperaquine, a reduced elimination clearance (41%) and a slower absorption (32%) of ivermectin was identified, resulting in higher exposures. Different peripheral volume of distributions of ivermectin in men and women were also observed (75% higher in females). Individual pharmacokinetic profiles were incorporated in a sigmoidal E max model, which were used to quantify the relationship between ivermectin exposure and mosquito-lethal effects. The integrated models described successfully the observed mortality of both Anopheles dirus and An. minimus . The final models were used to illustrate the potential impact on vector-control associated with ivermectin administration. In conclusion, ivermectin and its metabolites showed effective mosquito-lethal effects. The developed pharmacometric framework could be a useful tool in the evaluation of ivermectin as a potential vector-control agent in malaria elimination campaigns.
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Related topics: Malaria Research and Control · Parasitic Diseases Research and Treatment · Helminth infection and control
Thai researcher and institutional participation
Richard M. Hoglund · Kevin C. Kobylinski · Podjanee Jittamala · Borimas Hanboonkunupakarn · Narenrit Wamaket · Patchara Sriwichai · Siriporn Phasomkusolsil · Nicholas J. White · Nicholas P. J. Day · Joel Tarning · Mahidol Oxford Tropical Medicine Research Unit · Mahidol University · Armed Forces Research Institute of Medical Science
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