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dc.contributor.author
Wiens, Matthew O.  
dc.contributor.author
Kanters, Steve  
dc.contributor.author
Mills, Edward  
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Peregrina Lucano, Alejandro A.  
dc.contributor.author
Gold, Silvia  
dc.contributor.author
Ayers, Dieter  
dc.contributor.author
Ferrero, Luis  
dc.contributor.author
Krolewiecki, Alejandro Javier  
dc.date.available
2017-12-27T18:21:41Z  
dc.date.issued
2016-12  
dc.identifier.citation
Gold, Silvia; Peregrina Lucano, Alejandro A.; Mills, Edward; Kanters, Steve; Krolewiecki, Alejandro Javier; Ferrero, Luis; et al.; Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 60; 12; 12-2016; 7035-7042  
dc.identifier.issn
0066-4804  
dc.identifier.uri
http://hdl.handle.net/11336/31684  
dc.description.abstract
Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the elimination rate constant (kel), the absorption rate constant (Ka), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and Cmax were 51.31 mg · h/liter (95% credible interval [CrI], 45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1 (95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
American Society for Microbiology  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Benznidazole  
dc.subject
Chagas Disease  
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Pharmacokinetics  
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Meta-Analysis  
dc.subject.classification
Salud Ocupacional  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2017-09-01T18:03:53Z  
dc.journal.volume
60  
dc.journal.number
12  
dc.journal.pagination
7035-7042  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Washington  
dc.description.fil
Fil: Wiens, Matthew O.. University of British Columbia; Canadá  
dc.description.fil
Fil: Kanters, Steve. Precision Global Health;  
dc.description.fil
Fil: Mills, Edward. Mc Master University; Canadá  
dc.description.fil
Fil: Peregrina Lucano, Alejandro A.. Universidad de Guadalajara; México  
dc.description.fil
Fil: Gold, Silvia. Fundación Mundo Sano; Argentina  
dc.description.fil
Fil: Ayers, Dieter. Precision Global Health;  
dc.description.fil
Fil: Ferrero, Luis. Fundación Mundo Sano; Argentina  
dc.description.fil
Fil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina  
dc.journal.title
Antimicrobial Agents and Chemotherapy  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118981/  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.01567-16