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 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).
Li
Qigui
Q
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. qigui.li@amedd.army.mil
Cantilena
Louis R
LR
Leary
Kevin J
KJ
Saviolakis
George A
GA
Miller
R Scott
RS
Melendez
Victor
V
Weina
Peter J
PJ
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077332:Artesunate; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate