An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations
Article first published online: 7 JUL 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 1, pages 56–62, January 2013
How to Cite
Dinter, D., Gajski, G. and Garaj-Vrhovac, V. (2013), An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations. J. Appl. Toxicol., 33: 56–62. doi: 10.1002/jat.1711
- Issue published online: 29 NOV 2012
- Article first published online: 7 JUL 2011
- Manuscript Revised: 20 MAY 2011
- Manuscript Accepted: 20 MAY 2011
- Manuscript Received: 12 APR 2011
- clinically relevant concentrations;
- human peripheral blood lymphocytes;
- comet assay
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. Copyright © 2011 John Wiley & Sons, Ltd.