The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day per...

Currently recommended prophylactic regimens for Plasmodium falciparum malaria are associated with a high incidence of adverse events and/or suboptimal efficacy. In a double-blind, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of atovaquone/proguanil hydrochloride (250 mg/100 mg per tablet) to eliminate preexisting infection. Immedia...

A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquon...

After the remission of symptoms and reduction in spleen size while on proguanil therapy four patients with the tropical splenomegaly syndrome defaulted from treatment. The withdrawal of proguanil caused a recrudescence of original symptoms, splenomegaly, and a return of the initially raised serum IgM. Complete return to normal values was again effected with proguanil therapy.The role of the spl...

We have observed 4 French travelers, returning from African countries, who were not immune to malaria and were receiving chloroquine-proguanil prophylaxis, in whom the diagnosis of malaria could easily have been missed because the clinical signs were uncommon. These cases suggest that chloroquine-proguanil prophylaxis is not always effective and that travelers with unexplained symptoms should b...

Proguanil in combination with its synergistic partner atovaquone has been used for malaria treatment and prophylaxis decades. However mode of action is not fully understood. Here we yeast to investigate activity. inhibits growth, causes cell death acts synergy atovaquone. It was previously proposed that the drug would target system maintains mitochondrial membrane potential when respiratory cha...

CYP2C19 is a polymorphic enzyme which metabolizes several clinically important drugs including proguanil. Variation in the 5' regulatory region may influence CYP2C19 activity. This study evaluates the relationship between proguanil metabolic ratio and genetic variations of CYP2C19 in a South Indian population. Fifty unrelated healthy subjects were genotyped for CYP2C19 (*)2 and (*)3 alleles and...

Recently, it was reported that sera from healthy volunteers given atovaquone-proguanil (Malarone) inhibited parasite transmission and asexual blood stage development for up to 6 weeks after treatment (1). The lengthy persistence of drug activity was quite unexpected because earlier studies had shown that proguanil and atovaquone had elimination halflives of about 14 to 20 h (2–4, 10, 11) and 2 ...

OBJECTIVES A systematic review and meta-analysis of the effectiveness of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against malaria. METHODS The data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the ch...

Contributors: HTOD and TGR designed the study; C-LH collected the data and did the analysis; HTOD led on writing the paper, with substantial contributions from TGR and C-LH. HTOD acts as guarantor. Funding: Nuffield Trust, London, and the Commonwealth Fund, New York. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to pu...