Abstract
Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.
Trypanosoma cruzi; Chagas disease; Ketoconazole
An experimental and clinical assay with ketoconazole in the treatment of Chagas disease
Zigman Brener1
Joaquim Romeu Cançado2
Lucia Maria da Cunha Galvao1
Zélia Maria Profeta Luz1
Leny de Sousa Filardi1
Maria Elizabeth Soares Pereira1
Luiz Mauro T. Santos1
Catarina B. Cançado1
FIOCRUZ, Centro de Pesquisas René Rachou, Belo Horizonte, Brasil
Universidade Federal de Minas Gerais, Faculdade de Medicina, Belo Horizonte, Brasil
Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.
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Publication Dates
-
Publication in this collection
01 June 2009 -
Date of issue
Mar 1993
