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. The American journal of tropical medicine and hygiene [Am J Trop Med Hyg] Journal article

Title	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.
Author(s)	Li Q, Cantilena LR, Leary KJ, Saviolakis GA, Miller RS, Melendez V, Weina PJ
Institution	Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. qigui.li@amedd.army.mil
Source	Am J Trop Med Hyg 2009 Oct; 81(4):615-21.
MeSH	Adolescent Adult Antimalarials Area Under Curve Artemisinins Dose-Response Relationship, Drug Female Humans Injections, Intravenous Male Middle Aged Young Adult
Abstract	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 (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).
Language	eng
Pub Type(s)	Clinical Trial, Phase I Journal Article Randomized Controlled Trial Research Support, U.S. Gov't, Non-P.H.S.
PubMed ID	19815876

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