Split dosing of artemisinins does not improve antimalarial therapeutic efficacy
It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infecti...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2017
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| _version_ | 1826280572638461952 |
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| author | White, N Watson, J Ashley, E |
| author_facet | White, N Watson, J Ashley, E |
| author_sort | White, N |
| collection | OXFORD |
| description | It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates. To test these various hypotheses we performed a logistic meta-regression analysis of cure rates from all falciparum malaria treatment trials (n = 40) with monotherapy arms containing artemisinin or a derivative (76 arms). There was no evidence that split dosing enhanced cure rates. |
| first_indexed | 2024-03-07T00:15:42Z |
| format | Journal article |
| id | oxford-uuid:7ac5b4ff-fd19-4fd2-a664-c3c96045397f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:15:42Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:7ac5b4ff-fd19-4fd2-a664-c3c96045397f2022-03-26T20:46:12ZSplit dosing of artemisinins does not improve antimalarial therapeutic efficacyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7ac5b4ff-fd19-4fd2-a664-c3c96045397fEnglishSymplectic Elements at OxfordNature Publishing Group2017White, NWatson, JAshley, EIt has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates. To test these various hypotheses we performed a logistic meta-regression analysis of cure rates from all falciparum malaria treatment trials (n = 40) with monotherapy arms containing artemisinin or a derivative (76 arms). There was no evidence that split dosing enhanced cure rates. |
| spellingShingle | White, N Watson, J Ashley, E Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title | Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title_full | Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title_fullStr | Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title_full_unstemmed | Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title_short | Split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
| title_sort | split dosing of artemisinins does not improve antimalarial therapeutic efficacy |
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