MALARIA: The rise and fall of the antimalarial Lapdap: a lesson in pharmacogenetics

13 September 2010
The Lancet, Volume 376, Issue 9742, 28 August 2010-3 September 2010, Pages 739-741Prof Lucio Luzzatto MD

The spread of chloroquine-resistant Plasmodium falciparum in Africa has been a strong stimulus to the development of new antimalarial drugs. Although artemisinin and related compounds have been promising therapies since the 1980s, their low availability and high cost have greatly delayed large-scale use. In the meantime, a logical alternative was to experiment with existing agents, and there was added pressure to do so because of the increasing frequency of resistance to sulfadoxine-pyrimethamine (Fansidar, Roche, Basel, Switzerland), which was the main alternative to chloroquine. Therefore, in the late 1990s, a combination of chlorproguanil (Lapudrine) and dapsone—both low-cost drugs—known as Lapdap (GlaxoSmithKline, London, UK) was introduced. Chlorproguanil, which is similar to proguanil, is a very effective antimalarial, and dapsone, which is chemically related to the sulphonamides, is very effective for treatment of leprosy. Chlorproguanil and dapsone both interfere with folate metabolism but at different biosynthetic stages, thus their combined use was in line with the classic tenet of antimicrobial therapy, which aims to prevent development of resistant organisms.
http://www.malarianexus.com/articles/read/81/the-rise-and-fall-of-the-antimalarial-lapdap-a-lesson-in-pharmacogenetics/