The emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need increase arsenal new antimalarials with novel mechanisms action. To help achieve this aim, study tested potency three Malaria Box compounds (MMV006087, MMV085203, MMV008956) against five laboratory strains twenty clinical isolates Plasmodium falciparum using optimized in vitro growth inhib...

Chloroquine resistance in Plasmodium falciparum is primarily conferred by mutations in pfcrt. Parasites resistant to chloroquine can display hypersensitivity to other antimalarials; however, the patterns of crossresistance are complex, and the genetic basis has remained elusive. We show that stepwise selection for resistance to amantadine or halofantrine produced previously unknown pfcrt mutati...

INTRODUCTION Although the government of Yemen changed the national policy for treating malaria in November 2005 from chloroquine to combination drugs in the form of artesunate + sulphadoxine-pyrimethamine (SP) as first line and lumefantrine + artemether as second line treatment for uncomplicated malaria, clinicians in public and private health facilities continued to prescribe chloroquine becau...

Introduction Malaria in very young children is a major therapeutic challenge in highly endemic areas where initial infection can occur in the first few months of life. Because active immunity has not begun to be established, infants are most at risk from falciparum malaria, and it has been estimated by the World Health Organisation that up to 1096 of all infant mortality in Africa is directly o...

Mefloquine is a quinoline antimalarial drug that is structurally related to the antiarrhythmic agent quinidine. Mefloquine is widely used in both the treatment and prophylaxis of Plasmodium falciparum malaria. Mefloquine can prolong cardiac repolarization, especially when coadministered with halofantrine, an antagonist of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. For these...

The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (C(max)), were expressed as the fold of that particular effect with respect to their C(max). The following tests were used at 37 °C: hE...

Lariam (pharmacological name mefloquine) is an antimalaria drug discovered by the US Army shortly after the Vietnam War, and subsequently marketed worldwide by F. Hoffmann-La Roche. The first reported trials of mefloquine were in prisoners, and were performed at the Joliet Correctional Center, Illinois, in 1975, and at the Maryland House of Correction in 1976.1,2 Halfan (pharmacological name ha...

The influence of the size and turnover kinetics of the enterocyte-based lymph lipid precursor pool (LLPP) on intestinal lymphatic drug transport has been examined. Mesenteric lymph duct-cannulated rats were infused intraduodenally with low (2-5 mg/h) or high (20 mg/h) lipid-dose formulations containing 100 microg/h halofantrine (Hf, a model drug) and 1 microCi/h (14)C-oleic acid (OA) (as a mark...