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 Google Scholar
Google Scholar
Right arrow Articles by Mariga, S. T.
Right arrow Articles by Björkman, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mariga, S. T.
Right arrow Articles by Björkman, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2004, p. 4089-4096, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4089-4096.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Synergism between Amodiaquine and Its Major Metabolite, Desethylamodiaquine, against Plasmodium falciparum In Vitro

S. T. Mariga,1 J. P. Gil,1 C. Sisowath,1 W. H. Wernsdorfer,2 and A. Björkman1*

Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden,1 Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, Vienna, Austria2

Received 27 October 2003/ Returned for modification 3 December 2003/ Accepted 26 May 2004

The in vitro activity of the prodrug amodiaquine and its metabolite monodesethyl-amodiaquine has been studied for three strains of Plasmodium falciparum: LS-2, LS-3, and LS-1. Both compounds showed significant activity against all three strains; the activity of amodiaquine was slightly higher than that of the metabolite. By use of a checkerboard design, interaction studies with both compounds yielded evidence of significant synergism; means of the sums of the fractional inhibitory concentrations were 0.0392 to 0.0746 for strain LS-2, 0.1567 to 0.3102 for strain LS-3, and 0.025 to 0.3369 for strain LS-1. In further investigations, the interaction of amodiaquine with monodesethyl-amodiaquine was tested at clinically relevant concentrations of both compounds. In these studies, involving amodiaquine at picomolar and femtomolar concentrations, the compound was found to exert high potentiating activity on monodesethyl-amodiaquine. This interaction produced mean ratios of observed to expected activity of 0.0505 to 0.0642 for strain LS-2, 0.0882 to 0.3820 for strain LS-3, and 0.0752 to 0.2924 for strain LS-1. The synergistic activity was most marked at monodesethyl-amodiaquine/amodiaquine ratios up to 100,000:1 but was still evident at higher ratios.

* Corresponding author. Mailing address: Department of Infectious Diseases, Karolinska Hospital, Stockholm 17176, Sweden. Phone: 46 8 51771866. Fax: 46 8 51771806. E-mail: anders.bjorkman{at}kus.se.

Antimicrobial Agents and Chemotherapy, November 2004, p. 4089-4096, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4089-4096.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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