Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

Hdl Handle:
http://hdl.handle.net/10144/18902
Title:
Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.
Authors:
Checchi, F; Piola, P; Fogg, C; Bajunirwe, F; Biraro, S; Grandesso, F; Ruzagira, E; Babigumira, J; Kigozi, I; Kiguli, J; Kyomuhendo, J; Ferradini, L; Taylor, W R J; Guthmann, J P
Journal:
Malaria Journal
Abstract:
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.
Affiliation:
Epicentre, Paris, France. francesco.checchi@lshtm.ac.uk
Publisher:
BioMed Central
Issue Date:
2006
URI:
http://hdl.handle.net/10144/18902
DOI:
10.1186/1475-2875-5-59
PubMed ID:
16854236
Additional Links:
http://www.malariajournal.com
Language:
en
ISSN:
1475-2875
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorChecchi, F-
dc.contributor.authorPiola, P-
dc.contributor.authorFogg, C-
dc.contributor.authorBajunirwe, F-
dc.contributor.authorBiraro, S-
dc.contributor.authorGrandesso, F-
dc.contributor.authorRuzagira, E-
dc.contributor.authorBabigumira, J-
dc.contributor.authorKigozi, I-
dc.contributor.authorKiguli, J-
dc.contributor.authorKyomuhendo, J-
dc.contributor.authorFerradini, L-
dc.contributor.authorTaylor, W R J-
dc.contributor.authorGuthmann, J P-
dc.date.accessioned2008-02-21T16:41:00Z-
dc.date.available2008-02-21T16:41:00Z-
dc.date.issued2006-
dc.identifier.citationSupervised 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.en
dc.identifier.issn1475-2875-
dc.identifier.pmid16854236-
dc.identifier.doi10.1186/1475-2875-5-59-
dc.identifier.urihttp://hdl.handle.net/10144/18902-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.publisherBioMed Central-
dc.relation.urlhttp://www.malariajournal.com-
dc.rightsArchived on this site by Open Access permissionen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAmbulatory Careen
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshDirectly Observed Therapyen
dc.subject.meshDrug Administration Scheduleen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshEthanolaminesen
dc.subject.meshFemaleen
dc.subject.meshFluorenesen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMultivariate Analysisen
dc.subject.meshPatient Complianceen
dc.subject.meshRecurrenceen
dc.subject.meshTreatment Outcomeen
dc.subject.meshUgandaen
dc.titleSupervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.en
dc.contributor.departmentEpicentre, Paris, France. francesco.checchi@lshtm.ac.uken
dc.identifier.journalMalaria Journalen

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