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 op...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1797077729416314880 |
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| author | Ashley, E Stepniewska, K Lindegårdh, N Mcgready, R Annerberg, A Hutagalung, R Singtoroj, T Hla, G Brockman, A Proux, S Wilahphaingern, J Singhasivanon, P White, N Nosten, F |
| author_facet | Ashley, E Stepniewska, K Lindegårdh, N Mcgready, R Annerberg, A Hutagalung, R Singtoroj, T Hla, G Brockman, A Proux, S Wilahphaingern, J Singhasivanon, P White, N Nosten, F |
| author_sort | Ashley, E |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:22:09Z |
| format | Journal article |
| id | oxford-uuid:7cec3823-828d-460c-ae65-75581e021deb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:22:09Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:7cec3823-828d-460c-ae65-75581e021deb2022-03-26T21:00:03ZPharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7cec3823-828d-460c-ae65-75581e021debEnglishSymplectic Elements at Oxford2007Ashley, EStepniewska, KLindegårdh, NMcgready, RAnnerberg, AHutagalung, RSingtoroj, THla, GBrockman, AProux, SWilahphaingern, JSinghasivanon, PWhite, NNosten, F 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. |
| spellingShingle | Ashley, E Stepniewska, K Lindegårdh, N Mcgready, R Annerberg, A Hutagalung, R Singtoroj, T Hla, G Brockman, A Proux, S Wilahphaingern, J Singhasivanon, P White, N Nosten, F Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria. |
| title | 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_short | 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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