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Lumefantrine and Desbutyl-Lumefantrine Population Pharmacokinetic-Pharmacodynamic Relationships in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria on the Thailand-Myanmar Border

Kloprogge, F; McGready, R; Hanpithakpong, W; Blessborn, D; Day, NP; White, NJ; Nosten, F; (2015) 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 , 59 (10) pp. 6375-6384. 10.1128/AAC.00267-15. Green open access

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Abstract

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 desbutyl-lumefantrine 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].).

Type: Article
Title: Lumefantrine and Desbutyl-Lumefantrine Population Pharmacokinetic-Pharmacodynamic Relationships in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria on the Thailand-Myanmar Border
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/AAC.00267-15
Publisher version: http://doi.org/10.1128/AAC.00267-15
Language: English
Additional information: Copyright © 2015, Kloprogge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.
Keywords: Adolescent, Adult, Antimalarials, Computer Simulation, Drug Administration Schedule, Ethanolamines, Female, Fluorenes, Humans, Malaria, Falciparum, Models, Statistical, Myanmar, Plasmodium falciparum, Pregnancy, Recurrence, Thailand, Treatment Outcome
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
URI: https://discovery.ucl.ac.uk/id/eprint/1540017
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