Byakika-Kibwika, PaulineLamorde, MohammedMayito, JonathanNabukeera, LillianMayanja-Kizza, HarrietKatabira, EllyWarunee Hanpithakpongวารุณี หาญพิทักษ์พงศ์Obua, CelestinoPakker, NadineLindegardh, NiklasTarning, Joelde Vries, Peter J.Merry, ConceptaMahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.2014-06-302016-09-212014-06-302016-09-2120122014-06-252012-04-27Byakika-Kibwika P. et al. Pharmacokinetics and pharmacodynamics of intravenous artesunateduring severe malaria treatment in Ugandan adults. Malar J. 2012 Apr 27;11:132.1475-2875 (electronic)https://repository.li.mahidol.ac.th/handle/20.500.14594/661BACKGROUND: 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.engMahidol UniversityArtesunateIntravenousPharmacodynamicsPharmacokineticsSevere malariaOpen Access articleResearch ArticleBioMed Central10.1186/1475-2875-11-132