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Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments
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نویسنده
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diniz l.f. ,urbina j.a. ,de andrade i.m. ,mazzeti a.l. ,martins t.f. ,caldas i.s. ,talvani a. ,ribeiro i. ,bahia m.t.
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منبع
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plos neglected tropical diseases - 2013 - دوره : 7 - شماره : 8
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چکیده
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Background:current chemotherapy for chagas disease is unsatisfactory due to its limited efficacy,particularly in the chronic phase,with frequent side effects that can lead to treatment discontinuation. combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. we evaluated the efficacy of posaconazole in combination with benznidazole on trypanosoma cruzi infection in vivo.methods and findings:benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. using a rapid treatment protocol for 7 days,the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone,with the effects most evident in combinations of sub-optimal doses of the drugs. subsequently,the curative action of these drug combinations was investigated,using the same infection model and 25,50,75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5,10 or 20 mpk of posaconazole,given alone or concomitantly for 20 days. the effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses,indicating synergistic activity. finally,sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days),followed by the second drug administered for the same period of time. it was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone,and no cure was observed for the short treatments with drugs given alone.conclusions:our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds,and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of chagas disease. © 2013 diniz et al.
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آدرس
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laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, instituto venezolano de investigaciones científicas,caracas, Venezuela, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil, drugs for neglected diseases initiative,geneva, Switzerland, laboratório de doença de chagas,departamento de ciências biológicas and nucleo de pesquisas em ciencias biologicas,universidade federal de ouro preto,ouro preto,minas gerais, Brazil
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Authors
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