The efficacy of atovaquone and sulfadiazine was examined alone or in combination for the treatment of mice infected with six Brazilian Toxoplasma gondii strains previously genotyped using the PCR-RFLP assays of the SAG2 gene, in addition to RH strain. Swiss mice were infected intraperitoneally with 10(2) tachyzoites from each strain of T. gondii and treated with 6.25, 12.5, 25 and 50 mg/Kg/day ...

Atovaquone is a new anti-malarial agent that specifically targets the cytochrome bc1 complex and inhibits parasite respiration. A growing number of failures of this drug in the treatment of malaria have been genetically linked to point mutations in the mitochondrial cytochrome b gene. To better understand the molecular basis of atovaquone resistance in malaria, we introduced five of these mutat...

Tumour hypoxia renders cancer cells resistant to cancer therapy, resulting in markedly worse clinical outcomes. To find clinical candidate compounds that reduce hypoxia in tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify a number of drugs with this property. For this study we focus on the anti-malarial, atovaquone. Atovaquone rapidly decrease...

Thirty-eight of 295 subjects participating in a randomized, double-blind, placebo-controlled trial of the efficacy of daily administration of atovaquone/proguanil for malaria prevention developed malaria at some time during the 20-week prophylaxis period. These subjects (3 atovaquone/proguanil recipients and 35 placebo recipients) were treated with 4 tablets of atovaquone/proguanil per day for ...

Immunocompromised patients are at risk of developing toxoplasma encephalitis (TE). Standard therapy regimens (including sulfadiazine plus pyrimethamine) are hampered by severe side effects. While atovaquone has potent in vitro activity against Toxoplasma gondii, it is poorly absorbed after oral administration and shows poor therapeutic efficacy against TE. To overcome the low absorption of atov...

The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). ...

Atovaquone is used as a fixed-dose combination with proguanil (Malarone) for treating children and adults with uncomplicated malaria or as chemoprophylaxis for preventing malaria in travellers. Indeed, in the USA, between 2009 and 2011, Malarone prescriptions accounted for 70% of all antimalarial pre-travel prescriptions. In 2013 the patent for Malarone will expire, potentially resulting in a w...

Acute therapy with pyrimethamine plus sulfadiazine is the treatment of choice for reactivated toxoplasmic encephalitis (TE). Acute therapy is followed by lifelong maintenance therapy (secondary prophylaxis) with the same drugs at lower dosages. The use of pyrimethamine plus sulfadiazine is hampered by severe side effects including allergic reactions and hematotoxicity. Alternative treatment reg...

The aim of this work was to develop a new pharmaceutical form of atovaquone and to study its activity against Toxoplasma gondii in vitro and in vivo. Nanocapsules were chosen as the oral dosage form of administration. An analytical method was developed to determine the drug content in nanocapsules. The stability of these nanocapsules were assessed by following drug content, size, pH and osmolar...

Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is usually directly linked to the mitochondrial respiratory chain. Antimalarial naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting electron transport. Since atovaquone also has therapeutic activity against Pneumocystis carinii, the P. carinii DHOD may also be an important drug target. Orga...