Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria
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 ope...
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th-mahidol.245892018-08-24T09:10:42Z Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria 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 Immunology and Microbiology Medicine 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. 2018-08-24T01:54:39Z 2018-08-24T01:54:39Z 2007-02-01 Article Tropical Medicine and International Health. Vol.12, No.2 (2007), 201-208 10.1111/j.1365-3156.2006.01785.x 13653156 13602276 2-s2.0-33846952552 https://repository.li.mahidol.ac.th/handle/123456789/24589 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33846952552&origin=inward |
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Immunology and Microbiology Medicine 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 |
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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. |
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Shoklo Malaria Research Unit |
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Shoklo Malaria Research Unit 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 |
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Article |
author |
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 |
author_sort |
Elizabeth A. Ashley |
title |
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
title_short |
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
title_full |
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
title_fullStr |
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
title_full_unstemmed |
Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
title_sort |
pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/24589 |
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1763491474784124928 |