Publication: Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria
Issued Date
2007-02-01
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ISSN
13653156
13602276
13602276
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2-s2.0-33846952552
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Mahidol University
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SCOPUS
Bibliographic Citation
Tropical Medicine and International Health. Vol.12, No.2 (2007), 201-208
Suggested Citation
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 Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria. Tropical Medicine and International Health. Vol.12, No.2 (2007), 201-208. doi:10.1111/j.1365-3156.2006.01785.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24589
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Title
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria
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.