Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria
Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 pat...
| Príomhchruthaitheoirí: | , , , , , , , , , , , , , , , , , , , , , , |
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| Formáid: | Journal article |
| Teanga: | English |
| Foilsithe / Cruthaithe: |
American Society for Microbiology
2020
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| _version_ | 1826285206365011968 |
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| author | Wattanakul, T Ogutu, B Kabanywanyi, AM Asante, K-P Oduro, A Adjei, A Sie, A Sevene, E Macete, E Compaore, G Valea, I Osei, I Winterberg, M Gyapong, M Adjuik, M Abdulla, S Owusu-Agyei, S White, NJ Day, NPJ Tinto, H Baiden, R Binka, F Tarning, J |
| author_facet | Wattanakul, T Ogutu, B Kabanywanyi, AM Asante, K-P Oduro, A Adjei, A Sie, A Sevene, E Macete, E Compaore, G Valea, I Osei, I Winterberg, M Gyapong, M Adjuik, M Abdulla, S Owusu-Agyei, S White, NJ Day, NPJ Tinto, H Baiden, R Binka, F Tarning, J |
| author_sort | Wattanakul, T |
| collection | OXFORD |
| description | Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456 ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern. (This study has been registered at ClinicalTrials.gov under identifier NCT02199951.) |
| first_indexed | 2024-03-07T01:25:22Z |
| format | Journal article |
| id | oxford-uuid:91cb1d2f-a8be-459d-99bd-4b008cf2f65f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:25:22Z |
| publishDate | 2020 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:91cb1d2f-a8be-459d-99bd-4b008cf2f65f2022-03-26T23:21:08ZPooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum MalariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:91cb1d2f-a8be-459d-99bd-4b008cf2f65fEnglishSymplectic ElementsAmerican Society for Microbiology2020Wattanakul, TOgutu, BKabanywanyi, AMAsante, K-POduro, AAdjei, ASie, ASevene, EMacete, ECompaore, GValea, IOsei, IWinterberg, MGyapong, MAdjuik, MAbdulla, SOwusu-Agyei, SWhite, NJDay, NPJTinto, HBaiden, RBinka, FTarning, JDihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456 ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern. (This study has been registered at ClinicalTrials.gov under identifier NCT02199951.) |
| spellingShingle | Wattanakul, T Ogutu, B Kabanywanyi, AM Asante, K-P Oduro, A Adjei, A Sie, A Sevene, E Macete, E Compaore, G Valea, I Osei, I Winterberg, M Gyapong, M Adjuik, M Abdulla, S Owusu-Agyei, S White, NJ Day, NPJ Tinto, H Baiden, R Binka, F Tarning, J Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title | Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title_full | Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title_fullStr | Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title_full_unstemmed | Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title_short | Pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in African patients with uncomplicated falciparum Malaria |
| title_sort | pooled multicenter analysis of cardiovascular safety and population pharmacokinetic properties of piperaquine in african patients with uncomplicated falciparum malaria |
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