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

Abstract

Background: 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 (824) hours. Median (range) maximal artesunate concentration (C max ) was 3260 (1020164000) ng/mL, terminal elimination half-life (T was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290111256) ngh/mL. Median (range) dihydroartemisinin C max was 3140 (16709530) ng/mL, with T max of 0.14 (0.6 6.07) hours and Tof 1.31 (0.82.8) hou rs. Dihydroartemisinin AUC was 3492 (21836338) ngh/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. © 2012 Byakika-Kibwika et al.