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
<h4>Background</h4> <p>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 mefloqu...
| Main Authors: | , , |
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| Format: | Journal article |
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BioMed Central
2018
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| _version_ | 1826275721999286272 |
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| author | Hoglund, R Ruengweerayut, R Na-Bangchang, K |
| author_facet | Hoglund, R Ruengweerayut, R Na-Bangchang, K |
| author_sort | Hoglund, R |
| collection | OXFORD |
| description | <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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).</p> <h4>Conclusion</h4> <p>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.</p> |
| first_indexed | 2024-03-06T23:03:06Z |
| format | Journal article |
| id | oxford-uuid:62db2da0-ea6f-4842-b462-95618b6bf724 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:03:06Z |
| publishDate | 2018 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:62db2da0-ea6f-4842-b462-95618b6bf7242022-03-26T18:08:58ZPopulation 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 borderJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:62db2da0-ea6f-4842-b462-95618b6bf724Symplectic Elements at OxfordBioMed Central2018Hoglund, RRuengweerayut, RNa-Bangchang, K <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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).</p> <h4>Conclusion</h4> <p>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.</p> |
| spellingShingle | Hoglund, R Ruengweerayut, R Na-Bangchang, K 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
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