Absence of an interaction between artesunate and atovaquone - proguanil

Objective: Atovaquone plus proguanil is a new, well-tolerated and highly ef fective antimalarial drug. In order to protect it from the development of r esistance, it may be deployed in combination with an artemisinin derivative . To investigate whether artesunate affects the pharmacokinetics of atovaqu one plus proguanil, and to provide preliminary information regarding the to lerability of the triple drug combination (artesunate plus atovaquone plus proguanil), a cross over study was conducted in adult volunteers. Methods: Twelve healthy Karen adults were randomised to receive atovaquone- proguanil (1000/400 mg) with or without artesunate (250 mg) and, at least 9 0 days later, the study was repeated. Blood was sampled over a 10-day perio d. Results: The three-drug combination was well tolerated. Artesunate did not alter the pharmacokinetic properties of atovaquone and proguanil (maximum p lasma concentrations: 13.02 mu g/ml and 742 ng/ml; elimination half-lives: 42.2 h and 14.4 h; oral plasma clearance estimates: 90 ml/h/kg and 710 ml/h /kg; and apparent volumes of distribution: 4.9 l/kg and 14.5 l/kg, respecti vely). There was also no effect of artesunate on the biotransformation of p roguanil to cycloguanil. The pharmacokinetic variables were similar to thos e reported previously for the individual drugs. Conclusion: Artesunate does not influence atovaquone or proguanil pharmacok inetics. The triple-drug combination of atovaquone and proguanil and artesu nate was well tolerated.