In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum.

Abstract

Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern. We tested in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.

• Authors: Andrea Kreidenweiss, Peter G Kremsner, Klaus Dietz, Benjamin Mordmüller
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 75 Issue 6 Pg. 1178-81 (Dec 2006) ISSN: 0002-9637 [Print] United States
• PMID: 17172389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Antimalarials
• Ferrous Compounds
• Metallocenes
• Chloroquine
• ferroquine

Topics

• Aminoquinolines (pharmacology)
• Animals
• Antimalarials (pharmacology)
• Blood (parasitology)
• Chloroquine (pharmacology)
• Drug Evaluation, Preclinical
• Drug Resistance
• Ferrous Compounds (pharmacology)
• Humans
• Malaria, Falciparum (blood, parasitology)
• Metallocenes
• Parasitemia (blood)
• Plasmodium falciparum (drug effects, isolation & purification)