Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

soy2015_1847.pdf (167.13 KB)

Document type

Article

Version

Accepted version

Publication date

2015-03-30

All rights reserved

Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/99515

Population pharmacokinetics of benznidazole in adult patients with Chagas disease

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

http://dx.doi.org/10.1128/AAC.05018-14

Abstract

AIM: To build a population pharmacokinetic (PopPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. METHODS: Prospective, open-label, single-center clinical trial(EudraCT:2011-002900-34;CINEBENZclinicaltrials.govnumber:NCT01755403), approved by the local ethics committee. Patients received 2.5mg/kg/12h (Abarax(R), Elea Laboratory, Argentina) for 60 days. Plasma BZN samples were taken at several times along the study and analyzed by HPLC-UV. The PopPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion and residual variability were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate the BNZ concentration-time course profile for different dosage regimens. RESULTS: A total of 358 plasma BZN concentrations from 39 patients were included in the analysis. A one-compartment-PK-model characterized by clearance(CL/F) and apparent volume of distribution(V/F) with first order absorption(Ka) and elimination, adequately described the data (CL/F:1.73 L/h; V/F:89.6 L; Ka:1.15 h-1). No covariates were found to be significant for CL/F and V/F. Internal and external validation of the final model showed adequate results. Data from simulations revealed that a dose of 2.5mg/kg/12h might lead to overexposure in the most of the patients. A lower dose (2.5mg/kg/24h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3-6 mg/L. CONCLUSION: A population PK model for BNZ in adults with chronic Chagas disease has been developed. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24h would adequately keep BNZ trough plasma concentrations within the recommended target range concentrations for the majority of patients.

Subject

Malaltia de Chagas, Malalties parasitàries

Subject (English)

Chagas' disease, Parasitic diseases

Citation

Collections

Articles publicats en revistes (ISGlobal)

Citation

SOY MUNER, Dolors, et al. Population pharmacokinetics of benznidazole in adult patients
                with Chagas disease. Antimicrobial Agents and Chemotherapy. 2015. Vol. 59, num. 6, pags. 3342-3349. ISSN 0066-4804. [consulted: 17 of August of 2026]. Available at: https://hdl.handle.net/2445/99515

Export metadata

JSON - METS

Share record