دورية أكاديمية
Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice.
| العنوان: | Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice. |
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| المؤلفون: | Perin L; Laboratório de Pesquisas Clínicas, Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Moreira da Silva R; Núcleo de Pesquisas em Produtos Naturais e Sintéticos, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil., Fonseca KD; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Cardoso JM; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Mathias FA; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Reis LE; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Molina I; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Tropical Medicine and International Health Unit, Department of Infectious Diseases, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, PROSICS Barcelona, Barcelona, Spain., Correa-Oliveira R; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil., Vieira PM; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Laboratório de Morfopatologia, Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Carneiro CM; Laboratório de Pesquisas Clínicas, Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil carneirocm@gmail.com.; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Departamento de Análises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. |
| المصدر: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2017 Mar 24; Vol. 61 (4). Date of Electronic Publication: 2017 Mar 24 (Print Publication: 2017). |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, American Society for Microbiology |
| مواضيع طبية MeSH: | Nitroimidazoles/*blood , Trypanocidal Agents/*blood, Administration, Oral ; Adolescent ; Adult ; Animals ; Chagas Disease/blood ; Chagas Disease/drug therapy ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Mice ; Nitroimidazoles/pharmacokinetics ; Nitroimidazoles/therapeutic use ; Trypanocidal Agents/pharmacokinetics ; Trypanocidal Agents/therapeutic use ; Trypanosoma cruzi/drug effects ; Trypanosoma cruzi/pathogenicity ; Young Adult |
| مستخلص: | Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquid-liquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 μg/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 μg/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease. (Copyright © 2017 American Society for Microbiology.) |
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| فهرسة مساهمة: | Keywords: Chagas disease; Trypanosoma cruzi; benznidazole |
| المشرفين على المادة: | 0 (Nitroimidazoles) 0 (Trypanocidal Agents) YC42NRJ1ZD (benzonidazole) |
| تواريخ الأحداث: | Date Created: 20170208 Date Completed: 20170925 Latest Revision: 20240325 |
| رمز التحديث: | 20240325 |
| مُعرف محوري في PubMed: | PMC5365712 |
| DOI: | 10.1128/AAC.02410-16 |
| PMID: | 28167558 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-6596 |
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| DOI: | 10.1128/AAC.02410-16 |