Modelagem farmacocinética baseada em fisiologia do metilfenidato em adultos

Abstract

Introduction: Methylphenidate (MPH) is a psychotropic stimulant drug used as first pharmacological choice for treating Attention/Hyperactivity Deficit Disorder (ADHD). However, problems related to their use make further investigation of their pharmacokinetics (PK) in treating ADHD in the adult population needed. Physiology-based Pharmacokinetic modeling (PBPK) is a mathematical approach that aims to simulate concentration profiles versus time for different administration pathways integrating the physiological structure of a particular species and physicochemical characteristics of a compound. PK-Sim® is free opensource software developed by Open Systems Pharmacology (OSP) to construct full-body PBPK models. It can be used to simulate different species, characterizing their respective organisms in different biological compartments. Objective: The central objective of this work was to evaluate the variability of exposure after the use of MPH in adults. Methodology: A PBPK model for MPH was developed in PK-Sim® software (version 11.2) using information obtained from Literature on MPH, adult individuals, and two types of formulations. Results and Discussion: A PBPK model has been developed and validated whose predictive performance adequately meets the predefined criteria PK characteristics in Caucasian individuals and in a Caucasian population using a modified release formulation. Complementarily, a PK-Sim® - based tutorial was developed to enable readers to perform a PBPK analysis to provide a mechanistic approach to study and predict the PK of compounds based on the physiological and anatomical characteristics of a population of interest, as well as in the physical and chemical properties of a certain drug, as well as encouraging the production and teaching of Pharmaceutical Sciences among Portuguese speakers. Conclusion: This study properly verified the variability of exposure to MPH use in human adults. In addition, it also produced a Portuguese tutorial guiding PBPK modeling using PK-Sim® .