Journal article
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
- Abstract:
- Background Low 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. Methods A 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. Results Population 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 (Cmax) and elimination half-life (t1/2) were found in patients who had treatment failure (36 cases) compared to patients with successful treatment (107 cases). Conclusion The 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1186/s12936-018-2466-3
Authors
+ Thammasat University
More from this funder
- Grant:
- CenterofExcellenceinPharmacology
- MolecularBiologyofMalaria
- Cholangiocarcinoma
- Publisher:
- BioMed Central
- Journal:
- Malaria Journal More from this journal
- Volume:
- 322
- Issue:
- 17
- Publication date:
- 2018-09-03
- Acceptance date:
- 2018-08-27
- DOI:
- EISSN:
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1475-2875
- Keywords:
- Pubs id:
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pubs:924303
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uuid:532327f2-c93b-443b-9206-613de8748eec
- Local pid:
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pubs:924303
- Source identifiers:
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924303
- Deposit date:
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2018-10-08
Terms of use
- Copyright holder:
- Hoglund et al
- Copyright date:
- 2018
- Notes:
- © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Licence:
- CC Attribution (CC BY)
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