Publication: Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects
Issued Date
2019-01-01
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ISSN
15326535
00099236
00099236
DOI
Other identifier(s)
2-s2.0-85077397164
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Pharmacology and Therapeutics. (2019)
Suggested Citation
Kevin C. Kobylinski, Podjanee Jittamala, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Kanchana Pantuwatana, Siriporn Phasomkusolsil, Silas A. Davidson, Markus Winterberg, Richard M. Hoglund, Mavuto Mukaka, Rob W. van der Pluijm, Arjen Dondorp, Nicholas P.J. Day, Nicholas J. White, Joel Tarning Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects. Clinical Pharmacology and Therapeutics. (2019). doi:10.1002/cpt.1716 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/52374
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Title
Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects
Abstract
© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin-piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito-lethal effect across all subjects. Exposure to piperaquine was also increased when coadministered with ivermectin, but electrocardiograph QT-interval prolongation was not increased. One subject had transiently impaired liver function. Ivermectin mosquito-lethal effect was greater than predicted previously against the major Southeast Asian malaria vectors. Both Anopheles dirus and Anopheles minimus mosquito mortality was increased substantially (20-fold and 35-fold increase, respectively) when feeding on volunteer blood after ivermectin administration compared with in vitro ivermectin-spiked blood. This suggests the presence of ivermectin metabolites that impart mosquito-lethal effects. Further studies of this combined approach to accelerate malaria elimination are warranted.