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

Byakika-Kibwika, P; Lamorde, M; Mayito, J; Nabukeera, L; Mayanja-Kizza, H; Katabira, E; Hanpithakpong, W; Obua, C; Pakker, N; Lindegardh, N; Tarning, J; de Vries, P; Merry, C

Journal article

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 (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.

Publication status:: Published

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APA Style

Byakika-Kibwika, P., Lamorde, M., Mayito, J., Nabukeera, L., Mayanja-Kizza, H., Katabira, E., Hanpithakpong, W., Obua, C., Pakker, N., Lindegardh, N., Tarning, J., de Vries, P., & Merry, C. (2012). Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults. Malaria Journal, 11(1), 132.

MLA Style

Byakika-Kibwika, P, et al. “Pharmacokinetics and Pharmacodynamics of Intravenous Artesunate during Severe Malaria Treatment in Ugandan Adults.” Malaria Journal, vol. 11, no. 1, 2012, p. 132.

Chicago Style

Byakika-Kibwika, P, M Lamorde, J Mayito, et al. 2012. “Pharmacokinetics and Pharmacodynamics of Intravenous Artesunate during Severe Malaria Treatment in Ugandan Adults.” Malaria Journal 11 (1): 132.
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