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dc.contributor.authorByakika-Kibwika, Pauline
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorMayito, Jonathan
dc.contributor.authorNabukeera, Lillian
dc.contributor.authorMayanja-Kizza, Harriet
dc.contributor.authorKatabira, Elly
dc.contributor.authorHanpithakpong, Warunee
dc.contributor.authorObua, Celestino
dc.contributor.authorPakker, Nadine
dc.contributor.authorLindegardh, Niklas
dc.contributor.authorTarning, Joel
dc.contributor.authorde Vries, Peter J
dc.contributor.authorMerry, Concepta
dc.date.accessioned2012-11-05T12:03:29Z
dc.date.available2012-11-05T12:03:29Z
dc.date.issued2012-04-27
dc.identifier.citationMalaria Journal. 2012 Apr 27;11(1):132
dc.identifier.urihttp://dx.doi.org/10.1186/1475-2875-11-132
dc.identifier.urihttp://hdl.handle.net/10147/250931
dc.description.abstractAbstractBackgroundSevere malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria.MethodsFourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).ResultsAll study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8–24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020–164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290–111256) ng·h/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670–9530) ng/mL, with Tmax of 0.14 (0.6 – 6.07) hours and T1/2 of 1.31 (0.8–2.8) hours. Dihydroartemisinin AUC was 3492 (2183–6338) ng·h/mL. None of the participants reported adverse events.ConclusionsPlasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.
dc.titlePharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults
dc.typeJournal Article
dc.language.rfc3066en
dc.rights.holderPauline Byakika-Kibwika et al.; licensee BioMed Central Ltd.
dc.description.statusPeer Reviewed
dc.date.updated2012-11-05T12:02:42Z
refterms.dateFOA2018-08-23T01:19:40Z
html.description.abstractAbstractBackgroundSevere malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria.MethodsFourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).ResultsAll study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8–24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020–164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290–111256) ng·h/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670–9530) ng/mL, with Tmax of 0.14 (0.6 – 6.07) hours and T1/2 of 1.31 (0.8–2.8) hours. Dihydroartemisinin AUC was 3492 (2183–6338) ng·h/mL. None of the participants reported adverse events.ConclusionsPlasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.


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