Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers
<p>AIMS: The aims of the presented study were to evaluate the pharmacokinetic properties of dihydroartemisinin and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers.</p><p> MET...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2017
|
| _version_ | 1826300130579447808 |
|---|---|
| author | Chotsiri, P Wattanakul, T Hoglund, R Hanboonkunupakarn, B Pukrittayakamee, S Blessborn, D Jittamala, P White, N Day, N Tarning, J |
| author_facet | Chotsiri, P Wattanakul, T Hoglund, R Hanboonkunupakarn, B Pukrittayakamee, S Blessborn, D Jittamala, P White, N Day, N Tarning, J |
| author_sort | Chotsiri, P |
| collection | OXFORD |
| description | <p>AIMS: The aims of the presented study were to evaluate the pharmacokinetic properties of dihydroartemisinin and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers.</p><p> METHODS: Population pharmacokinetic properties of dihydroartemisinin and piperaquine were assessed in 16 in healthy Thai adults using an open-label randomized crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling. </p><p>RESULTS: The developed models described dihydroartemisinin and piperaquine population pharmacokinetics accurately. Concomitant treatment with primaquine did not affect the pharmacokinetic properties of dihydroartemisinin or piperaquine. A linear pharmacokinetic-pharmacodynamic model described satisfactorily the relationship between the individually corrected QT-intervals and piperaquine concentrations; the population mean QT-interval increased by 4.17 ms per 100 ng/mL increase in piperaquine plasma concentration. Simulations from the final model showed that monthly and bi-monthly mass drug administration in healthy subjects would result in median maximum QT-interval prolongations of 18.9 and 16.8 ms, respectively, and would be very unlikely to result in prolongation of more than 50 ms. A single low dose of primaquine can be added safely to the existing dihydroartemisinin-piperaquine treatment in areas of multi-resistant falciparum malaria.</p><p> CONCLUSIONS: Pharmacokinetic-pharmacodynamic modelling and simulation in healthy adult volunteers suggested that therapeutic doses of DHA-piperaquine in prevention or treatment are very unlikely to be associated with dangerous QT-prolongation.</p> |
| first_indexed | 2024-03-07T05:12:29Z |
| format | Journal article |
| id | oxford-uuid:dc090fcf-bdc2-400f-9316-db9bb3db7af7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:12:29Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:dc090fcf-bdc2-400f-9316-db9bb3db7af72022-03-27T09:14:57ZPopulation pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dc090fcf-bdc2-400f-9316-db9bb3db7af7EnglishSymplectic Elements at OxfordWiley2017Chotsiri, PWattanakul, THoglund, RHanboonkunupakarn, BPukrittayakamee, SBlessborn, DJittamala, PWhite, NDay, NTarning, J<p>AIMS: The aims of the presented study were to evaluate the pharmacokinetic properties of dihydroartemisinin and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers.</p><p> METHODS: Population pharmacokinetic properties of dihydroartemisinin and piperaquine were assessed in 16 in healthy Thai adults using an open-label randomized crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling. </p><p>RESULTS: The developed models described dihydroartemisinin and piperaquine population pharmacokinetics accurately. Concomitant treatment with primaquine did not affect the pharmacokinetic properties of dihydroartemisinin or piperaquine. A linear pharmacokinetic-pharmacodynamic model described satisfactorily the relationship between the individually corrected QT-intervals and piperaquine concentrations; the population mean QT-interval increased by 4.17 ms per 100 ng/mL increase in piperaquine plasma concentration. Simulations from the final model showed that monthly and bi-monthly mass drug administration in healthy subjects would result in median maximum QT-interval prolongations of 18.9 and 16.8 ms, respectively, and would be very unlikely to result in prolongation of more than 50 ms. A single low dose of primaquine can be added safely to the existing dihydroartemisinin-piperaquine treatment in areas of multi-resistant falciparum malaria.</p><p> CONCLUSIONS: Pharmacokinetic-pharmacodynamic modelling and simulation in healthy adult volunteers suggested that therapeutic doses of DHA-piperaquine in prevention or treatment are very unlikely to be associated with dangerous QT-prolongation.</p> |
| spellingShingle | Chotsiri, P Wattanakul, T Hoglund, R Hanboonkunupakarn, B Pukrittayakamee, S Blessborn, D Jittamala, P White, N Day, N Tarning, J Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title | Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title_full | Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title_fullStr | Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title_full_unstemmed | Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title_short | Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers |
| title_sort | population pharmacokinetics and electrocardiographic effects of dihydroartemisinin piperaquine in healthy volunteers |
| work_keys_str_mv | AT chotsirip populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT wattanakult populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT hoglundr populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT hanboonkunupakarnb populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT pukrittayakamees populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT blessbornd populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT jittamalap populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT whiten populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT dayn populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers AT tarningj populationpharmacokineticsandelectrocardiographiceffectsofdihydroartemisininpiperaquineinhealthyvolunteers |