Population pharmacokinetics of orally administrated bromopride: Focus on the absorption process

• Published in: European journal of pharmaceutical sciences 2020-01, Vol.142, p.105081, Article 105081
• Main Authors: Lachi-Silva, Larissa, Barth, Aline B., Santos, Gustavo Mendes Lima, Ahamadi, Malidi, Bruschi, Marcos Luciano, Kimura, Elza, de Araújo, Bibiana Verlindo, Diniz, Andréa
• Format: Article
• Language: English
• Subjects: Absorption models; Bromopride; Model selection; Monolix; Nonlinear mixed-effects modeling; Solid dosage forms
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105081

Bromopride is a prokinetic and antiemetic drug used to treat nausea and vomiting. Although its prescription is common in Brazil, there is a lack of studies about bromopride pharmacokinetics. Therefore, the aims of this study were to investigate the population pharmacokinetics of bromopride and to evaluate the influence of covariates on its absorption. This study is a retrospective analysis of data collected from bioequivalence studies. The data was modeled using MONOLIX 2018R2. Assuming one-compartment and linear elimination, the absorption phase was evaluated with different structural models. The model of sequential first- and zero-order with combined error and exponential inter-individual variability in all parameters best described the atypical absorption profile of bromopride. Population estimates were first-order absorption rate (ka) of 0.08 h − 1, fraction of dose absorbed by first-order (Fr) of 32.60%, duration of the zero-order absorption (Tk0) of 0.88 h with latency time (Tlag) of 0.47 h, volume of distribution of 230 l and clearance of 46.80 l h − 1. Bodyweight affects Tk0, dosage form was found to correlate with Tk0 and Tlag, while gender affects Tlag. However, simulations evaluating the clinical importance of these covariates on steady-state indicated minimal changes on bromopride exposure. The mixed absorption model was reasonable to describe the absorption process of bromopride because it had the flexibility to fit multiple-peaks profile and shows good agreement with physicochemical properties of drug. [Display omitted]