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-->infinity)) 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) microg/ml h, compared with 432 (308-992) microg/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.
RCT Entities:
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-->infinity)) 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) microg/ml h, compared with 432 (308-992) microg/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.
Authors: Selidji T Agnandji; Florian Kurth; Jose F Fernandes; Solange S Soulanoudjingar; Beatrice P Abossolo; Ghyslain Mombo-Ngoma; Arti Basra; Raquel González; Gondo Kizito; Pembe I Mayengue; Lorenz Auer-Hackenberg; Saadou Issifou; Bertrand Lell; Ayola A Adegnika; Michael Ramharter Journal: Malar J Date: 2011-12-14 Impact factor: 2.979
Authors: Joel Tarning; Rose McGready; Niklas Lindegardh; Elizabeth A Ashley; Mupawjay Pimanpanarak; Benjamas Kamanikom; Anna Annerberg; Nicholas P J Day; Kasia Stepniewska; Pratap Singhasivanon; Nicholas J White; François Nosten Journal: Antimicrob Agents Chemother Date: 2009-06-29 Impact factor: 5.191
Authors: Sam Salman; Madhu Page-Sharp; Susan Griffin; Kaye Kose; Peter M Siba; Kenneth F Ilett; Ivo Mueller; Timothy M E Davis Journal: Antimicrob Agents Chemother Date: 2011-08-29 Impact factor: 5.191
Authors: Muhammad Ntale; Celestino Obua; Jackson Mukonzo; Margarita Mahindi; Lars L Gustafsson; Olof Beck; Jasper W Ogwal-Okeng Journal: Malar J Date: 2009-03-30 Impact factor: 2.979