Publication: Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults
Issued Date
2012-06-19
Resource Type
ISSN
14752875
Other identifier(s)
2-s2.0-84862176876
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Mahidol University
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SCOPUS
Bibliographic Citation
Malaria Journal. Vol.11, (2012)
Suggested Citation
Pauline Byakika-Kibwika, Mohammed Lamorde, Jonathan Mayito, Lillian Nabukeera, Harriet Mayanja-Kizza, Elly Katabira, Warunee Hanpithakpong, Celestino Obua, Nadine Pakker, Niklas Lindegardh, Joel Tarning, Peter J. De Vries, Concepta Merry Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults. Malaria Journal. Vol.11, (2012). doi:10.1186/1475-2875-11-132 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14302
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Title
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.