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Am. J. Trop. Med. Hyg., 75(5), 2006, pp. 817-826
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

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THE EVALUATION OF RADIOLABELED ARTESUNATE ON TISSUE DISTRIBUTION IN RATS AND PROTEIN BINDING IN HUMANS

QIGUI LI*, LISA H. XIE, ADAM HAEBERLE, JING ZHANG, AND PETER WEINA
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland

The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [14C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat and human plasma. Radioactivity and drug levels in blood, plasma, tissues, urine, and feces up to 192 hours were collected and measured. The mean terminal half-life of plasma (76 h) and blood (105 h) radioactivity was prolonged compared with that of unchanged AS (0.43 h) and dihydroartemisinin (0.75 h), an active metabolite of AS. Drug was widely distributed after 1 hour in select tissues. After 24 hours, the radioactivity rapidly declined in all tissues except spleen until 96 hours. Only 1% of total radioactivity was detected in brain tissue. AS revealed a higher binding capacity with human and rat plasma proteins (73–81%). The radioactivity in whole blood was higher (two to fourfold) than that in plasma throughout the period of the treatment, suggesting that AS binding to RBCs may relate to its powerful antimalarial activity.

Received March 16, 2006. Accepted for publication July 14, 2006.

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.

Financial support: This study was supported by the United States Army Research and Materiel Command.

* 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}na.amedd.army.mil

Authors’ addresses: Qigui Li, Lisa H. Xie, Adam Haeberle, Jing Zhang, and Peter Weina, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, Tel: (301) 319-9351, Fax: (301) 319-7360, E-mails: qigui.li{at}na.amedd.army.mil; lisa.xie{at}na.amedd.army.mil; adam.haeberle{at}na.amedd.army.mil; jing.zhang{at}na.amedd.army.mil; peter.weina{at}na.amedd.army.mil.

Reprint requests: Dr. Qigui Li, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. Tel: (301) 319-9351, Fax: (301) 319-7360, E-mail: qigui.li{at}na.amedd.army.mil.






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Copyright © 2006 by the American Society of Tropical Medicine and Hygiene.