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
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Angus, B. J.
Right arrow Articles by White, N. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Angus, B. J.
Right arrow Articles by White, N. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2002, p. 778-782, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.778-782.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Oral Artesunate Dose-Response Relationship in Acute Falciparum Malaria

Brian J. Angus,1,2 Itaporn Thaiaporn,3 Kenechanh Chanthapadith,1 Yupin Suputtamongkol,1 and Nicholas J. White1,2*

Faculty of Tropical Medicine, Mahidol University, Bangkok 10400,1 Sangklaburi Hospital, Sangklaburi, Kanchanaburi Province, Thailand,3 Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom2

Received 27 February 2001/ Returned for modification 18 August 2001/ Accepted 11 November 2001

The combination of an oral artemisinin derivative (usually artesunate) and mefloquine has become standard treatment for multidrug-resistant falciparum malaria in several parts of Southeast Asia. The doses of artesunate used in monotherapy and combination treatment have largely been derived empirically. In order to characterize the in vivo dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia >=1% were randomized to receive a single oral dose of artesunate varying between 0 and 250 mg together with a curative dose of oral mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic variable. An inhibitory sigmoidal maximum effect (Emax) pharmacodynamic model typical of a dose-response curve was fitted to the relationship between dose and shortening of parasite clearance time (PCT). The Emax was estimated as 28.6 oral h, and the 50% effective concentration was 1.6 mg/kg of body weight. These results imply that there is no reduction in PCTs with the use of single doses of artesunate higher than 2 mg/kg, and this therefore reflects the average lower limit of the maximally effective dose.

* Corresponding author. Mailing address: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Phone: (66-2) 246-0832. Fax: (66-2) 246-7795. E-mail: fnnjw{at}diamond.mahidol.ac.th.

Antimicrobial Agents and Chemotherapy, March 2002, p. 778-782, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.778-782.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nosten, F., White, N. J. (2007). Artemisinin-Based Combination Treatment of Falciparum Malaria. Am J Trop Med Hyg 77: 181-192 [Abstract] [Full Text]  
  • Karunajeewa, H. A., Reeder, J., Lorry, K., Dabod, E., Hamzah, J., Page-Sharp, M., Chiswell, G. M., Ilett, K. F., Davis, T. M. E. (2006). Artesunate Suppositories versus Intramuscular Artemether for Treatment of Severe Malaria in Children in Papua New Guinea. Antimicrob. Agents Chemother. 50: 968-974 [Abstract] [Full Text]  
  • Woodrow, C J, Haynes, R K, Krishna, S (2005). Artemisinins. Postgrad. Med. J. 81: 71-78 [Abstract] [Full Text]  
  • Karunajeewa, H. A., Ilett, K. F., Dufall, K., Kemiki, A., Bockarie, M., Alpers, M. P., Barrett, P. H., Vicini, P., Davis, T. M. E. (2004). Disposition of Artesunate and Dihydroartemisinin after Administration of Artesunate Suppositories in Children from Papua New Guinea with Uncomplicated Malaria. Antimicrob. Agents Chemother. 48: 2966-2972 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»