title: Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.
abstract: Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Campus Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Araraquara, São Paulo, Brazil davanco.marcelo@gmail.com peccinin@fcfar.unesp.br.
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: Davanço
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Campus Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Araraquara, São Paulo, Brazil.
authors.forename: Michel Leandro
authors.initials: ML
authors.lastname: Campos
authors.affiliation: Laboratório de Tecnologia dos Medicamentos (LTM), Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil.
authors.forename: Talita Atanazio
authors.initials: TA
authors.lastname: Rosa
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Campus Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Araraquara, São Paulo, Brazil.
authors.forename: Elias Carvalho
authors.initials: EC
authors.lastname: Padilha
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Campus Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Araraquara, São Paulo, Brazil.
authors.forename: Alejandro Henao
authors.initials: AH
authors.lastname: Alzate
authors.affiliation: Colegiado de Ciências Farmacêuticas, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina, Pernambuco, Brazil.
authors.forename: Larissa Araújo
authors.initials: LA
authors.lastname: Rolim
authors.affiliation: Laboratório de Tecnologia dos Medicamentos (LTM), Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil.
authors.forename: Pedro José
authors.initials: PJ
authors.lastname: Rolim-Neto
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Campus Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Araraquara, São Paulo, Brazil davanco.marcelo@gmail.com peccinin@fcfar.unesp.br.
authors.forename: Rosângela Gonçalves
authors.initials: RG
authors.lastname: Peccinini
mesh_terms: D000328:Adult; D000818:Animals; D000981:Antiprotozoal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D002648:Child; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male; D009593:Nitroimidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D012995:Solubility; D013607:Tablets; D014349:Trypanosoma cruzi
chemical_list: D000981:Antiprotozoal Agents; D003692:Delayed-Action Preparations; D009593:Nitroimidazoles; D013607:Tablets; C009999:benzonidazole