Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs
Issued Date
2023-07-18
Resource Type
eISSN
10986596
Scopus ID
2-s2.0-85164843339
Pubmed ID
37338381
Journal Title
Antimicrobial agents and chemotherapy
Volume
67
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial agents and chemotherapy Vol.67 No.7 (2023) , e0173022
Suggested Citation
Yipsirimetee A., Tipthara P., Hanboonkunupakarn B., Tripura R., Lek D., Kümpornsin K., Lee M.C.S., Sattabongkot J., Dondorp A.M., White N.J., Kobylinski K.C., Tarning J., Chotivanich K. Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs. Antimicrobial agents and chemotherapy Vol.67 No.7 (2023) , e0173022. doi:10.1128/aac.01730-22 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88081
Title
Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs
Other Contributor(s)
Abstract
Ivermectin is an endectocide used widely to treat a variety of internal and external parasites. Field trials of ivermectin mass drug administration for malaria transmission control have demonstrated a reduction of Anopheles mosquito survival and human malaria incidence. Ivermectin will mostly be deployed together with artemisinin-based combination therapies (ACT), the first-line treatment of falciparum malaria. It has not been well established if ivermectin has activity against asexual stage Plasmodium falciparum or if it interacts with the parasiticidal activity of other antimalarial drugs. This study evaluated antimalarial activity of ivermectin and its metabolites in artemisinin-sensitive and artemisinin-resistant P. falciparum isolates and assessed in vitro drug-drug interaction with artemisinins and its partner drugs. The concentration of ivermectin causing half of the maximum inhibitory activity (IC50) on parasite survival was 0.81 μM with no significant difference between artemisinin-sensitive and artemisinin-resistant isolates (P = 0.574). The ivermectin metabolites were 2-fold to 4-fold less active than the ivermectin parent compound (P < 0.001). Potential pharmacodynamic drug-drug interactions of ivermectin with artemisinins, ACT-partner drugs, and atovaquone were studied in vitro using mixture assays providing isobolograms and derived fractional inhibitory concentrations. There were no synergistic or antagonistic pharmacodynamic interactions when combining ivermectin and antimalarial drugs. In conclusion, ivermectin does not have clinically relevant activity against the asexual blood stages of P. falciparum. It also does not affect the in vitro antimalarial activity of artemisinins or ACT-partner drugs against asexual blood stages of P. falciparum.