Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data

Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration...

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Bibliographic Details
Published in:BMC medicine 2015-09, Vol.13 (1), p.227, Article 227
Main Authors: WorldWide Antimalarial Resistance Network (WWARN), Bassat Orellana, Quique
Format: Article
Language:English
Subjects:
Analysis
Antimalarials
Antimalarials - administration & dosage
Antimalarials - therapeutic use
Antiparasitic agents
Artemether
Artemisinins - therapeutic use
Care and treatment
Cerca documental en línia
Development and progression
Dose-Response Relationship, Drug
Drug dosages
Drug resistance
Drug Therapy, Combination
Ethanolamines - therapeutic use
Ethics
Fluorenes - therapeutic use
Genetic aspects
Health aspects
Humans
Lumefantrine
Malaria
Malaria, Falciparum - drug therapy
Malària
Medical research
Medicaments antipalúdics
Medicine, Experimental
Online bibliographic searching
Patient outcomes
Patients
Pharmacokinetics
Plasma
Plasmodium falciparum
Pregnancy
Prevention
Recurrence
Statistical analysis
Treatment Failure
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Summary:Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95% CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95% CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (98% cure rates (if parasitemia
ISSN:1741-7015
1741-7015
DOI:10.1186/s12916-015-0456-7