An experimental and clinical assay with ketoconazole in the treatment of Chagas disease.
Ketoconazole, an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanosoma 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 suppressive 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.
Brener
Z
Z
Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil.
Cançado
J R
JR
Galvão
L M
LM
da Luz
Z M
ZM
Filardi
L de S
Lde S
Pereira
M E
ME
Santos
L M
LM
Cançado
C B
CB
D000328:Adult; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D008148:Lovastatin / Q000627:therapeutic use; D051379:Mice; D009547:Nifurtimox / Q000627:therapeutic use; D009593:Nitroimidazoles / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects
D009593:Nitroimidazoles; D008148:Lovastatin; D009547:Nifurtimox; D007654:Ketoconazole; C009999:benzonidazole