ArticleMalaria journal2018
Population pharmacokinetics of mefloquine given as a 3-day artesunate-mefloquine in patients with acute uncomplicated Plasmodium falciparum malaria in a multidrug-resistant area along the Thai-Myanmar border.
Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Population Pharmacokinetics of Ensitrelvir in Healthy Participants and Participants with SARS-CoV-2 Infection in the SCORPIO-SR Study.Clinical pharmacokinetics · 2024Trial
- Translational Pharmacokinetic and Pharmacodynamic Evaluation of Mefloquine AgainstACS pharmacology & translational science · 2026Article
- Origin and Spread of Evolving Artemisinin-ResistantThe American journal of tropical medicine and hygiene · 2019Review
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow mefloquine exposure has been shown to contribute to treatment failure in patients with uncomplicated falciparum malaria following a 3-day artesunate-mefloquine combination. The present study aimed to develop a population pharmacokinetic model for mefloquine based on whole blood concentration-time profiles of this target population for further dose optimization.
methodsA total of 129 Burmese patients aged above 15 years who presented with typical symptoms of malaria and had a blood smear positive for Plasmodium falciparum were included in the study. All were treated with the standard 3-day combination regimen of artesunate and mefloquine consisting of mefloquine for 2 days and artesunate for 3 days. Blood samples were collected before and at different time points after drug administration from different sub-groups of patients. Mefloquine concentrations were quantified in whole blood using high-performance liquid chromatography. A non-linear mixed-effect modelling approach was applied for population pharmacokinetic analysis using the NONMEM v7.3 software. Covariates investigated (body weight, gender, admission parasitaemia, and molecular markers of mefloquine resistance) were investigated in a step-wise manner using the SCM functionality in Perl-Speaks-NONMEM.
resultsPopulation pharmacokinetic analysis of mefloquine was performed in all patients with a total of 653 samples. Whole blood mefloquine concentration-time profiles were described by a two-compartment disposition model. Of the covariates investigated, none was found to have a significant impact on the pharmacokinetics of mefloquine. Significant differences in maximum concentration (C
conclusionThe study successfully describes the pharmacokinetics of mefloquine following a 2-day treatment of mefloquine as a part of a 3-day artesunate-mefloquine in patients with uncomplicated falciparum malaria from Thailand. A model has been developed which adequately describes the pharmacokinetics of mefloquine. More extensive clinical studies including both adults and children are needed to fully characterize the pharmacokinetics of mefloquine.
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