ArticleAntimicrobial agents and chemotherapy2015
Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Population pharmacokinetic-pharmacodynamic analysis of benznidazole monotherapy and combination therapy with fosravuconazole in chronic Chagas disease (BENDITA).PLoS neglected tropical diseases · 2025Trial
- Beyond the catalysis of Trypanosoma cruzi trans-sialidases: structure, function, post-translational modifications, intrinsically disordered regions and use of CRISPR/Cas9.Archives of microbiology · 2026Review
- Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.PLoS neglected tropical diseases · 2025Article
- Review
- Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV‑2 Mpro).Scientific reports · 2024Article
- Fifteen Years after the Definition ofLife (Basel, Switzerland) · 2023Review
- Endogenous Sterol Synthesis Is Dispensable forFrontiers in microbiology · 2022Article
- Anti-International journal of molecular sciences · 2021Article
- Treatment With Suboptimal Dose of Benznidazole Mitigates Immune Response Molecular Pathways in Mice With Chronic Chagas Cardiomyopathy.Frontiers in cellular and infection microbiology · 2021Article
- Article
- Novel structural CYP51 mutation in Trypanosoma cruzi associated with multidrug resistance to CYP51 inhibitors and reduced infectivity.International journal for parasitology. Drugs and drug resistance · 2020Article
- Challenges in Chagas Disease Drug Development.Molecules (Basel, Switzerland) · 2020Review
- Inhibition of SREBP Improves Cardiac Lipidopathy, Improves Endoplasmic Reticulum Stress, and Modulates Chronic Chagas Cardiomyopathy.Journal of the American Heart Association · 2020Article
- Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069.PLoS neglected tropical diseases · 2020Article
- Efficacy of the Benznidazole+Posaconazole combination therapy in parasitemia reduction: An experimental murine model of acute Chagas.Revista da Sociedade Brasileira de Medicina Tropical · 2020Article
- A case report of long treatment with Itraconazole in a patient with chronic Chagas disease.BMC infectious diseases · 2019Article
- Therapeutic Interventions for Countering Leishmaniasis and Chagas's Disease: From Traditional Sources to Nanotechnological Systems.Pathogens (Basel, Switzerland) · 2019Review
- Triazolopyrimidines and Imidazopyridines: Structure-Activity Relationships and in Vivo Efficacy for Trypanosomiasis.ACS medicinal chemistry letters · 2019Article
- Search of Allosteric Inhibitors and Associated Proteins of an AKT-International journal of molecular sciences · 2018Article
- Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation-A histopathological study.International journal of experimental pathology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates.
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