Publication: Lumefantrine and desbutyl-lumefantrine population pharmacokinetic-pharmacodynamic relationships in pregnant women with uncomplicated Plasmodium falciparum malaria on the Thailand-Myanmar border
Issued Date
2015-10-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-84942866303
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.59, No.10 (2015), 6375-6384
Suggested Citation
Frank Kloprogge, Rose McGready, Warunee Hanpithakpong, Daniel Blessborn, Nicholas P.J. Day, Nicholas J. White, François Nosten, Joel Tarninga Lumefantrine and desbutyl-lumefantrine population pharmacokinetic-pharmacodynamic relationships in pregnant women with uncomplicated Plasmodium falciparum malaria on the Thailand-Myanmar border. Antimicrobial Agents and Chemotherapy. Vol.59, No.10 (2015), 6375-6384. doi:10.1128/AAC.00267-15 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/36309
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Title
Lumefantrine and desbutyl-lumefantrine population pharmacokinetic-pharmacodynamic relationships in pregnant women with uncomplicated Plasmodium falciparum malaria on the Thailand-Myanmar border
Abstract
Copyright © 2015, Kloprogge et al. Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than those of lumefantrine. Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand. A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border. The best model was used to evaluate therapeutic outcomes with a time-to-event approach. Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an Emax model, both predicted treatment outcomes, but lumefantrine provided better predictive power. A combined model including both lumefantrine and desbutyllumefantrine did not improve the model further. Simulations suggested that cure rates in pregnant women with falciparum malaria could be increased by prolonging the treatment course. (These trials were registered at controlled-trials.com [ISRCTN 86353884].)