Population pharmacokinetics of orally administrated bromopride: Focus on the absorption process
| Autor: | Gustavo Mendes Lima Santos, Elza Kimura, Marcos Luciano Bruschi, Malidi Ahamadi, Bibiana Verlindo de Araújo, Larissa Lachi-Silva, Aline Bergesch Barth, Andréa Diniz |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.drug_class Metoclopramide Pharmaceutical Science Administration Oral Biological Availability 02 engineering and technology Absorption (skin) Population pharmacokinetics Pharmacology Bioequivalence 030226 pharmacology & pharmacy Dosage form 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Bromopride medicine Antiemetic Humans Retrospective Studies Volume of distribution business.industry 021001 nanoscience & nanotechnology Kinetics Gastrointestinal Absorption Antiemetics Female 0210 nano-technology business Brazil medicine.drug |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 142 |
| ISSN: | 1879-0720 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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