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|Title:||Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.|
|Authors:||Checchi, Francesco;Piola, Patrice;Fogg, Carole;Bajunirwe, Francis;Biraro, Samuel;Grandesso, Francesco;Ruzagira, Eugene;Babigumira, Joseph;Kigozi, Isaac;Kiguli, James;Kyomuhendo, Juliet;Ferradini, Laurent;Taylor, Walter R J;Guthmann, Jean-Paul|
|subject:||Adolescent;Adult;Aged;Aged, 80 and over;Ambulatory Care;Animals;Antimalarials;Artemisinins;Children;Child, Preschool;Directly Observed Therapy;Drug Administration Schedule;Drug Therapy, Combination;Ethanolamines;Female;Fluorenes;Humans;Infant;Malaria, Falciparum;Male;Middle Aged;Multivariate Analysis;Patient Compliance;Recurrence;Treatment Outcome;Uganda|
|Description:||BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.|
|Standard no:||Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda. 2006, 5:59 Malar. J.|
|Appears in Collections:||Malaria|
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