Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 81, Issue 4, Pages 615-621Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.2009.09-0150
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Funding
- US Army Research and Material Command
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The pharmacokinetics of good manufacturing process injection of artesunate (AS) were evaluated after single closes at 0.5, 1, 2.4, and 8 mg/kg with a 2-minute infusion in 40 healthy subjects. Drug concentrations were analyzed by validated liquid chromatography and mass spectrometry system (LC-MS/MS) procedures. The drug was immediately converted to dihydroartemisinin (DHA), with elimination half-lives ranging 0.12-0.24 and 1.15-2.37 hours for AS and DHA. respectively. Pharmacokinetic model-dependent analysis is suitable for AS, whereas DHA fits both model-dependent and -independent methods. Although DHA concentration was superior to that of AS with a 1.12-1.87 ratio of area trader the curve (AUC)(DHA/AS), peak concentration of AS was much higher than that of DHA, with a 2.80- to 4.51-fold ratio of peak concentration (C-max AS/DHA). Therefore,AS effectiveness has been attributed not only to its rapid hydrolysis to DHA, but also to itself high initial C-max.
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