Population pharmacokinetic modeling of benznidazole in Brazilian patients with chronic Chagas disease

Abstract

The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.

Figure 1. Internal validation. Observed versus individual-predicted (top left) and population-predicted (top right) concentration diagnostic plots, visual predictive check. The figure presents the correlation between observed data (patients’ plasma concentrations) and predicted (model estimated) concentrations. The VPC compare the distribution of simulated observations with the distribution of measured observations in the population, 90% prediction intervals generated from the posterior predictions encompass 90% of the observations.