Avaliação da atividade terapêutica do itraconazol nas infecções crônicas, experimental e humana, pelo Trypanosoma cruzi

Abstract

Alguns pesquisadores demonstraram que o intraconzol, "in vitro" e na infecção aguda de animais, possui atividade antiparasitária referente ao Trypanosoma cruzi. Diante dessas observações, decidimos empreender estudo sobre e etapa crônica da parasitose devida a esse protozoário, considerando que ela é mais proeminente sob o ponto de vista médico-assistencial. A propósito, efetuamos apreciações baseadas em modelo composto por camundongos infectados e, também, relacionadas com indivíduos acometidos de doença de Chagas. Usamos 100 mg/kg/dia, por meio de sonda gástrica, durante três meses, e 100 ou 200 mg/dia, pela via oral, respectivamente, no decurso de igual período, sem evidenciarmos efeitos benéficos, pelo menos conforme a metodologia adotada

Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis: the results of clinical and parasitological examinations 11 years post-treatment

“…When Moreira et al (1992) treated Brazilian cases with itraconazole, however, they failed to detect any parasitological or clinical improvement, perhaps because they used a shorter treatment at lower doses ((200 mg/ day for 3 months, compared with about 400 mg/day used for 4 months in Chile). It is also possible that the predominant Try.…”

Parasitological cure of Chagas disease: is it possible? Is it relevant?

“…T. cruzi has also an absolute requirement of specific endogenous sterols for cell viability and proliferation and is extremely sensitive to sterol biosynthesis inhibitors (SBI) in vitro (Docampo et al 1981, Beach et al 1986, Goad et al 1989, Urbina et al 1988, 1993, 1996b; thus, the sterol biosynthesis pathway in this organism is a valid chemotherapeutic target (Urbina 1997). Nevertheless, currently available SBI's, such as ketoconazole and itraconazole, have been shown to be unable to eradicate T. cruzi from experimentally infected animals or human patients (McCabe 1988, Moreira et al 1992, Brener et al 1993, although a recent report from Chile claims a high level (>50%) of parasitological cures in chronic patients treated with itraconazole (Apt et al 1998). We have recently shown that fourth generation triazole derivatives, such as D0870 (Zeneca Pharmaceuticals) and SCH 56592 (Schering-Plough), are capable of inducing very high rates (70-100%) of parasitological cure in murine models of acute (short term) and chronic (long term) Chagas disease, while currently available drugs such as nifurtimox and ketoconazole had no significant curative activity in the same models (Urbina et al 1996a, 1998, Urbina 1997, Liendo et al 1998).…”

Activities of the Triazole Derivative SCH 56592 (Posaconazole) against Drug-Resistant Strains of the Protozoan Parasite Trypanosoma ( Schizotrypanum ) cruzi in Immunocompetent and Immunosuppressed Murine Hosts

“…Like many fungi and yeasts, T. cruzi has a strict requirement of specific endogenous sterols for cell viability and growth and is extremely sensitive to sterol biosynthesis inhibitors in vitro (13, 16, 29, 31-33, 35, 36). However, currently available sterol biosynthesis inhibitors, which are highly successful in the treatment of fungal diseases, are not powerful enough to eradicate T. cruzi from experimentally infected animals or human patients (3,18,20). Recent work from our laboratories has shown that new azole derivatives (inhibitors of fungal cytochrome P-450-dependent C 14 sterol demethylase), such as D0870 (Zeneca Pharmaceuticals) and SCH 56592 (Schering-Plough Research Institute, Kenilworth, N.J.), are capable of inducing parasitological cures in murine models of both acute and chronic Chagas' disease (13,29,30,33,34) and are the first compounds ever to display such activity.…”