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Antimicrobial Agents and Chemotherapy, March 2004, p. 954-960, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.954-960.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum-Based Bioassay for Measurement of Artemisinin Derivatives in Plasma or Serum

Paktiya Teja-Isavadharm,^1* James O. Peggins,^2, Thomas G. Brewer,^2, Nicholas J. White,^3,4 H. Kyle Webster,^1, and Dennis E. Kyle^1,2,¶

Armed Forces Research Institute of Medical Sciences,¹ Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,³ Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC,² Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom⁴

Received 3 April 2003/ Returned for modification 6 September 2003/ Accepted 18 November 2003

Artemisinin and its derivatives, artesunate and artemether, are rapidly acting antimalarials that are used for the treatment of severe and uncomplicated multidrug-resistant falciparum malaria. To optimize treatment regimens that use this new class of antimalarials, there is a need for readily available and reproducible assays to monitor drug levels closely in patients. A sensitive and reproducible bioassay for the measurement of the concentrations of artemisinin derivatives in plasma and serum is described. By modifying the in vitro drug susceptibility test, it was found that antimalarial activity in plasma or serum containing an unknown concentration of drug could be equated to the known concentrations of dihydroartemisinin (DHA) required to inhibit parasite growth. Dose-response curves for a Plasmodium falciparum clone (clone W2) and DHA were used as a standard for each assay. Assays with plasma or serum spiked with DHA proved to be reproducible (coefficient of variation, 10.9%), with a lower limit of quantitation equivalent to 2.5 ng of DHA per ml. For plasma spiked with artesunate or artemether, there was good agreement of the results obtained by the bioassay and the concentrations measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The bioassay for measurement of the antimalarial activities of artemisinin derivatives in body fluids requires a smaller volume of plasma or serum and is more sensitive than the presently available HPLC methods, can provide pharmacodynamic parameters for determination of activity against the parasite, and should enhance the design of more appropriate dosage regimens for artemisinin drugs.

Present address: Toxicology & Pharmacology Branch, Developmental Therapeutics Program, National Cancer Institute, Bethesda, MD 20892.

Present address: Global Health Program, Bill and Melinda Gates Foundation, Seattle, WA 98102.

Present address: Becton Dickinson Inc., San Jose, CA 95030.

^¶ Present address: Australian Army Malaria Institute, Enoggera, Brisbane, QLD 4051, Australia.

This article has been cited by other articles:

• Woodrow, C J, Haynes, R K, Krishna, S (2005). Artemisinins. Postgrad. Med. J. 81: 71-78 [Abstract] [Full Text]  
• Noedl, H., Teja-Isavadharm, P., Miller, R. S. (2004). Nonisotopic, Semiautomated Plasmodium falciparum Bioassay for Measurement of Antimalarial Drug Levels in Serum or Plasma. Antimicrob. Agents Chemother. 48: 4485-4487 [Abstract] [Full Text]