AJTMH Tropical Medicine and Hygiene News
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am. J. Trop. Med. Hyg., 81(4), 2009, pp. 615-621
doi:10.4269/ajtmh.2009.09-0150;
Copyright © 2009 by The American Society of Tropical Medicine and Hygiene

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Li, Q.
Right arrow Articles by Weina, P. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, Q.
Right arrow Articles by Weina, P. J.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

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

Qigui Li*, Louis R. Cantilena, Kevin J. Leary, George A. Saviolakis, R. Scott Miller, Victor Melendez, AND Peter J. Weina
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.

Received March 19, 2009. Accepted for publication June 29, 2009.

Financial support: This study was supported by the US Army Research and Material Command.

Disclaimer: The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting true views of the Department of the Army or the Department of Defense.

* Address correspondence to Qigui Li, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20307. E-mail: qigui.li{at}amedd.army.mil

Authors’ addresses: Qigui Li, Louis R. Cantilena, Kevin J. Leary, George A. Saviolakis, R. Scott Miller, Victor Melendez, and Peter Weina, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, and Division of Clinical Pharmacology and Medical Toxicology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD 20814, E-mails: qigui.li{at}amedd.army.mil, lcantilena{at}usuhs.mil, kevin.leary{at}amedd.army.mil, george.saviolakis{at}amedd.army.mil, robert.miller{at}amedd.army.mil, victor.melendez{at}amedd.army.mil, and peter.weina{at}amedd.army.mil.

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{at}amedd.army.mil.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society of Tropical Medicine and Hygiene.