Trial reportAntimicrobial agents and chemotherapy2010
Population pharmacokinetics and pharmacodynamics of artemether and lumefantrine during combination treatment in children with uncomplicated falciparum malaria in Tanzania.
Trial report in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.PLoS medicine · 2018Pooled it
- Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis.Malaria journal · 2015Pooled it
- Pooled it
- Efficacy of artemether-lumefantrine and artesunate-amodiaquine as first line therapy of uncomplicated malaria in Burkina Faso, 11 years after policy change.The Pan African medical journal · 2020Trial
- Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.The Journal of infectious diseases · 2016Trial
- Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in healthy adults.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetics and pharmacodynamics of oral artesunate monotherapy in patients with uncomplicated Plasmodium falciparum malaria in western Cambodia.Antimicrobial agents and chemotherapy · 2012Trial
- Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria.Malaria journal · 2011Trial
- Population pharmacokinetics of artemether, lumefantrine, and their respective metabolites in Papua New Guinean children with uncomplicated malaria.Antimicrobial agents and chemotherapy · 2011Trial
- Pharmacokinetic and pharmacodynamic characteristics of a new pediatric formulation of artemether-lumefantrine in African children with uncomplicated Plasmodium falciparum malaria.Antimicrobial agents and chemotherapy · 2011Trial
- Translation of a Human-Based Malaria-on-a-Chip Phenotypic Disease Model for In Vivo Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Artemisinin-resistant malaria.Clinical microbiology reviews · 2024Review
- Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar.Emerging infectious diseases · 2020Article
- Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development.Scientific reports · 2020Article
- Optimal Treatments for Severe Malaria and the Threat Posed by Artemisinin Resistance.The Journal of infectious diseases · 2019Article
- Population Pharmacokinetics of Artemether, Dihydroartemisinin, and Lumefantrine in Rwandese Pregnant Women Treated for Uncomplicated Plasmodium falciparum Malaria.Antimicrobial agents and chemotherapy · 2018Article
- Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling.Nature communications · 2017Article
- Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.Antimicrobial agents and chemotherapy · 2016Article
- Application of the Multistate Tuberculosis Pharmacometric Model in Patients With Rifampicin-Treated Pulmonary Tuberculosis.CPT: pharmacometrics & systems pharmacology · 2016Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
Abstract
The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one-compartment model. The pharmacokinetics of artemether was time dependent, with typical oral clearance increasing from 2.6 liters/h/kg on day 1 to 10 liters/h/kg on day 3. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of oral clearance was estimated to 77 ml/h/kg. The proposed semimechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However, the poor precision in some parameters illustrates the need for further data to support and refine this model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.