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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-132) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PBK, PJ D, CO and CM contributed to the design and conduct of the study. PBK, M L, JM and LN participated in recruitment of participants and data collection. WH and NL performed the bioanalytical assays. PBK, JT and NL analysed and interpreted the data. HMK, EK, NP, PJ D, and CM, participated in training the study staff and provided scientific support. PBK drafted the first version and all authors reviewed and approved the manuscript for submission.

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.
Zusatzmaterial
Authors’ original file for figure 1
12936_2011_2454_MOESM1_ESM.pdf
Authors’ original file for figure 2
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Authors’ original file for figure 3
12936_2011_2454_MOESM3_ESM.doc
Authors’ original file for figure 4
12936_2011_2454_MOESM4_ESM.doc
Authors’ original file for figure 5
12936_2011_2454_MOESM5_ESM.doc
Literatur
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