Atovaquone/proguanil for the treatment and prevention of malaria

Pearson, Richard D.

doi:10.1007/s11908-001-0058-8

Cited by 3 publications

(1 citation statement)

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“…Since malaria, which is caused by species of the parasite genus Plasmodium , remains a major global health problem, there are various drugs widely used in the prophylaxis and treatment of this disease, one of them being atovaquone, which usually comes in fixed combination with proguanil hydrochloride (Looareesuwan et al ., ; Olliaro, ; Patel and Kain, ; Pearson, ; Wiesner et al ., ). For the prevention of malaria in travelers, antimalarial agents should fulfil the requirements of efficacy towards the parasite, in addition to being safe for the consumer and not putting them at additional risk of adverse effects (Chattopadhyay et al ., ; Dhanawat et al ., ; Nzila and Chilengi, ).…”

Section: Introductionmentioning

confidence: 99%

An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations

Dinter

Gajski

Garaj‐Vrhovac

2011

J of Applied Toxicology

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Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages.

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