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

被引:26
作者
Byakika-Kibwika, Pauline [1 ,2 ,3 ]
Lamorde, Mohammed [1 ,2 ]
Mayito, Jonathan [3 ]
Nabukeera, Lillian [1 ]
Mayanja-Kizza, Harriet [1 ,3 ]
Katabira, Elly [1 ,3 ]
Hanpithakpong, Warunee [4 ]
Obua, Celestino [5 ]
Pakker, Nadine [3 ]
Lindegardh, Niklas [4 ,6 ]
Tarning, Joel [4 ,6 ]
de Vries, Peter J. [7 ]
Merry, Concepta [1 ,2 ,3 ]
机构
[1] Makerere Univ, Infect Dis Inst, Kampala, Uganda
[2] Trinity Coll Dublin, Dept Pharmacol & Therapeut, Dublin, Ireland
[3] Infect Dis Network Treatment & Res Africa, Kampala, Uganda
[4] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand
[5] Makerere Univ, Coll Hlth Sci, Dept Pharmacol & Therapeut, Kampala, Uganda
[6] Churchill Hosp, Ctr Clin Vaccinol & Trop Med, Oxford OX3 7LJ, England
[7] Univ Amsterdam, Acad Med Ctr, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands
基金
英国惠康基金;
关键词
Pharmacokinetics; Pharmacodynamics; Intravenous; Artesunate; Severe malaria; SEVERE FALCIPARUM-MALARIA; HEALTHY-VOLUNTEERS; RANDOMIZED-TRIAL; QUININE; ARTEMISININ;
D O I
10.1186/1475-2875-11-132
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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 (C-max) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T-1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ng.h/mL. Median (range) dihydroartemisinin C-max was 3140 (1670-9530) ng/mL, with T-max of 0.14 (0.6-6.07) hours and T-1/2 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.
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页数:6
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