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Pharmacokinetic Profiles of Artesunate After Single Intravenous Doses at 0.5, 1, 2, 4, and 8 mg/kg in Healthy Volunteers: A Phase I Study

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  • 1 Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Division of Clinical Pharmacology and Medical Toxicology, Uniformed Services University of the Health Sciences, Bethesda, Maryland

The pharmacokinetics of good manufacturing process injection of artesunate (AS) were evaluated after single doses 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 under 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 (Cmax AS/DHA). Therefore, AS effectiveness has been attributed not only to its rapid hydrolysis to DHA, but also to itself high initial Cmax.

Author Notes

Reprint requests: Qigui Li, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, E-mail: qigui.li@amedd.army.mil.
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