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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.accessioned2013-01-03T06:57:24Z
dc.date.available2013-01-03T06:57:24Z
dc.date.issued2012-04-27
dc.identifier.citationByakika-Kibwika, P., Lamorde, M., Mayito, J., Nabukeera, L., Mayanja-Kizza, H., Katabira, E., Hanpithakpong, W., Obua, C., Pakker, N., Lindegardh, N., Tarning, J., de Vries, P.J., Merry, C. (2012). Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults. Malaria Journal, 11(1)en_US
dc.identifier.issn1475-2875
dc.identifier.urihttp://www.malariajournal.com/content/11/1/132
dc.identifier.urihttp://hdl.handle.net/10570/942
dc.description.abstractBackground: Severe 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. Methods: Fourteen 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). Results: All 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. Conclusions: Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.en_US
dc.description.sponsorshipThe Infectious Diseases Network for Treatment and Research in Africa and the HIV Research Trust and Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme (077166/Z/05/Z) supported by the Wellcome Trust of Great Britain.en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.subjectPharmacokineticsen_US
dc.subjectPharmacodynamicsen_US
dc.subjectIntravenousen_US
dc.subjectArtesunateen_US
dc.subjectSevere malariaen_US
dc.subjectMalariaen_US
dc.subjectAntimalarial treatmenten_US
dc.subjectUgandaen_US
dc.subjectFalciparum malariaen_US
dc.titlePharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adultsen_US
dc.typeJournal article, peer revieweden_US


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