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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/24589
Title: Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria
Authors: Elizabeth A. Ashley
Kasia Stepniewska
Niklas Lindegårdh
Rose McGready
Anna Annerberg
Robert Hutagalung
Thida Singtoroj
Gilvary Hla
Al Brockman
Stephane Proux
Jahser Wilahphaingern
Pratap Singhasivanon
Nicholas J. White
François Nosten
Shoklo Malaria Research Unit
Mahidol University
Churchill Hospital
Menzies School of Health Research
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Feb-2007
Citation: Tropical Medicine and International Health. Vol.12, No.2 (2007), 201-208
Abstract: Background: Adherence to antimalarial drug regimens is improved by simple dosing. If the fixed antimalarial drug combination artemether-lumefantrine (AL) could be given once daily, this should improve adherence and thus effectiveness and lower the risk of selecting for resistance. Methods: In an open randomized study, 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days. The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves (AUC). Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles. Results: Lumefantrine pharmacokinetic profiles were obtained for 36 patients. The AUC(0→∞)of the once-daily regimen was 30% lower than that in the conventional regimen (P = 0.011) with a median (range) value of 306 (114-5781) μg/ml h, compared with 432 (308-992) μg/ml h. There was no significant difference in the peak plasma concentrations reached. PCR-adjusted cure rate estimates at day 42 of follow-up were 94% (95% CI: 84-100) in the six-dose arm and 85% (70-100) in the three-dose arm (P = 0.3). Conclusion: Artemether-lumefantrine efficacy is reduced by once-daily dosing, because absorption of lumefantrine is dose limited. At currently recommended doses, this antimalarial should be given twice daily in a 3-day regimen, with food containing fat. © 2007 Blackwell Publishing Ltd.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33846952552&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/24589
ISSN: 13653156
13602276
Appears in Collections:Scopus 2006-2010

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