Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults

Hdl Handle:
http://hdl.handle.net/10147/250931
Title:
Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults
Authors:
Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Mayanja-Kizza, Harriet; Katabira, Elly; Hanpithakpong, Warunee; Obua, Celestino; Pakker, Nadine; Lindegardh, Niklas; Tarning, Joel; de Vries, Peter J; Merry, Concepta
Citation:
Malaria Journal. 2012 Apr 27;11(1):132
Issue Date:
27-Apr-2012
URI:
http://dx.doi.org/10.1186/1475-2875-11-132; http://hdl.handle.net/10147/250931
Abstract:
AbstractBackgroundSevere 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.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
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-
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