Abstract
BackgroundSevere 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.
Highlights
Severe malaria is a medical emergency with high mortality
It is fundamental that plasma concentrations of a highly effective anti-malarial drug are achieved as rapidly as possible
Artesunate is a water-soluble hemisuccinate artemisinin derivative; available as sodium hemisuccinate salt for injection (Guilin Pharmaceutical Factory, Guangxi, People’s Republic of China). It has superior anti-malarial properties to quinine and artemether and studies have demonstrated a dramatic reduction in in-hospital mortality among children and adults treated with artesunate [2,3,4,5,6,7]
Summary
Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. Severe malaria is a medical emergency which if not treated results in 100% mortality. It is fundamental that plasma concentrations of a highly effective anti-malarial drug are achieved as rapidly as possible. Artesunate is a water-soluble hemisuccinate artemisinin derivative; available as sodium hemisuccinate salt for injection (Guilin Pharmaceutical Factory, Guangxi, People’s Republic of China). It has superior anti-malarial properties to quinine and artemether and studies have demonstrated a dramatic reduction in in-hospital mortality among children and adults treated with artesunate [2,3,4,5,6,7]. Artesunate’s excellent anti-malarial properties demonstrated by rapid parasite and fever clearance, is enhanced by its rapid hydrolysis to its active metabolite dihydroartemisinin [8,9,10,11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
