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In Vitro and in Vivo Effects of Itraconazole against Trypanosoma Cruzi

Robert E. McCabe^*,,, Jack S. Remington^*,, AND Fausto G. Araujo^*

^* Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 94301
Division of Infectious Diseases, Department of Medicine, Stanford University Medical Center, Stanford, California 94305

The synthetic imidazole, itraconazole, was examined for in vitro and in vivo activity against Trypanosoma cruzi. Mice treated with concentrations as low as 15 mg itraconazole/kg/day were completely protected against death due to infection with any of three different and highly virulent strains of T. cruzi. Treatment of infected mice with 120 mg itraconazole/kg/day for seven to nine weeks apparently resulted in the parasitologic cure as determined by negative hemocultures and subinoculations, negative serology for T. cruzi, and absence of parasites in histologic sections following completion of therapy. Peak serum levels of itraconazole after treatment of mice with the dose of the drug that provided protection against death were less than 1 µg/ml. Experiments in vitro revealed that concentrations of itraconazole as little as 0.001 µg/ml inhibited replication of intracellular amastigotes in macrophages. These results indicate that itraconazole has a remarkable activity against T. cruzi. Further investigation of intraconazole as a therapeutic agent for Chagas' disease may be warranted.

Accepted for publication October 11, 1985.

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