Pharmacokinetics of Benznidazole in experimental chronic Chagas Disease using the Swiss mouse-Berenice-78 Trypanosoma cruzi strain model.

Simple item page
dc.contributor.authorJesus, Suzana Marques de
dc.contributor.authorPinto, Leonardo Santos Ribeiro
dc.contributor.authorMoreira, Fernanda de Lima
dc.contributor.authorNardotto, Glauco Henrique Balthazar
dc.contributor.authorCristofoletti, Rodrigo
dc.contributor.authorMelo, Luísa Helena Perin de
dc.contributor.authorFonseca, Kátia da Silva
dc.contributor.authorBarbêdo, Pauliana
dc.contributor.authorBandeira, Lorena Cera
dc.contributor.authorVieira, Paula Melo de Abreu
dc.contributor.authorCarneiro, Cláudia Martins
dc.date.accessioned2022-04-05T14:28:17Z
dc.date.available2022-04-05T14:28:17Z
dc.date.issued2021pt_BR
dc.description.abstractChronic Chagas disease might have an impact on benznidazole pharmacokinetics with potential alterations in the therapeutic dosing regimen. This study aims to investigate the influence of chronic Trypanosoma cruzi infection on the pharmacokinetics and biodistribution of benznidazole in mice. Healthy (n= 40) and chronically T. cruzi (Berenice-78 strain)-infected (n= 40) Swiss female 10-month-old mice received a single oral dose of 100 mg/kg of body weight of benznidazole. Serial blood, heart, colon, and brain samples were collected up to 12 h after benznidazole administration. The serum and tissue samples were analyzed using a high-performance liquid chromatography instrument coupled to a diode array detector. Chronic infection by T. cruzi increased the values of the pharmacokinetic parameters absorption rate constant (Ka) (3.92 versus 1.82 h21 ), apparent volume of distribution (V/F) (0.089 versus 0.036 liters), and apparent clearance (CL/F) (0.030 versus 0.011 liters/h) and reduced the values of the time to the maximum concentration of drug in serum (Tmax) (0.67 versus 1.17 h) and absorption half-life (t1/2a) (0.18 versus 0.38 h). Tissue exposure (area under the concentration-versus-time curve from 0 h to time t for tissue [AUC0–t,tissue]) was longer and higher in the colon (8.15 versus 21.21mg · h/g) and heart (5.72 versus 13.58mg · h/g) of chronically infected mice. Chronic infection also increased the benznidazole tissue penetration ratios (AUC0–t,tissue/AUC0–t,serum ratios) of brain, colon, and heart by 1.6-, 3.25-, and 3-fold, respectively. The experimental chronic Chagas disease inflammationmediated changes in the regulation of membrane transporters probably influence the benznidazole pharmacokinetics and the extent of benznidazole exposure in tissues. These results advise for potential alterations in benznidazole pharmacokinetics in chronic Chagas disease patients with possibilities of changes in the standard dosing regimen.pt_BR
dc.identifier.citationJESUS, S. M. de et al. Pharmacokinetics of Benznidazole in experimental chronic Chagas Disease using the Swiss mouse-Berenice-78 Trypanosoma cruzi strain model. Antimicrobial Agents and Chemotherapy, v. 65, artigo e01383-20, fev. 2021. Disponível em: <https://journals.asm.org/doi/10.1128/AAC.01383-20?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed>. Acesso em: 10 jun. 2021.pt_BR
dc.identifier.doihttps://doi.org/10.1128/AAC.01383-20pt_BR
dc.identifier.issn1098-6596
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/14841
dc.identifier.uri2https://journals.asm.org/doi/10.1128/AAC.01383-20?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmedpt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectPreclinical drug studiespt_BR
dc.titlePharmacokinetics of Benznidazole in experimental chronic Chagas Disease using the Swiss mouse-Berenice-78 Trypanosoma cruzi strain model.pt_BR
dc.typeArtigo publicado em periodicopt_BR
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
ARTIGO_PharmacokineticsBenznidazoleExperimental.pdf
Size:
485.63 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
DECBI - Artigos publicados em periódicos