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Memórias do Instituto Oswaldo Cruz

Print version ISSN 0074-0276On-line version ISSN 1678-8060

Mem. Inst. Oswaldo Cruz vol.88 no.1 Rio de Janeiro Jan./Mar. 1993

http://dx.doi.org/10.1590/S0074-02761993000100023 

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

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.

Key words: Trypanosoma cruzi; Chagas disease; Ketoconazole

 

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