Publication: Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults.
Accepted Date
2012-04-27
Issued Date
2012-04-27
Copyright Date
2012
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Byakika-Kibwika P. et al. Pharmacokinetics and pharmacodynamics of intravenous artesunateduring severe malaria treatment in Ugandan adults. Malar J. 2012 Apr 27;11:132.
Suggested Citation
Byakika-Kibwika, Pauline, Lamorde, Mohammed, Mayito, Jonathan, Nabukeera, Lillian, Mayanja-Kizza, Harriet, Katabira, Elly, Warunee Hanpithakpong, วารุณี หาญพิทักษ์พงศ์, Obua, Celestino, Pakker, Nadine, Lindegardh, Niklas, Tarning, Joel, de Vries, Peter J., Merry, Concepta Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults.. Byakika-Kibwika P. et al. Pharmacokinetics and pharmacodynamics of intravenous artesunateduring severe malaria treatment in Ugandan adults. Malar J. 2012 Apr 27;11:132.. doi:10.1186/1475-2875-11-132 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/661
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Title
Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults.
Corresponding Author(s)
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
(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.