Modelagem farmacocinética para otimização de doses de gentamicina em cães

Abstract

Gentamicin is an aminoglycoside used to treat bacterial infections and is mainly used intravenously in hospitals. High concentrations of this drug can cause nephrotoxicity and ototoxicity. The aim of this study was to build pharmacokinetic models to predict the efficacy and risk of adverse effects of gentamicin doses in dogs. The first part of the study aimed to carry out this evaluation using a population pharmacokinetic model (popPK), which was built with Monolix software (Lixoft SAS, Simulations Plus Company), using raw data from a pharmacokinetic study carried out by Widerhon et al. In the second part of the study, efficacy and the risk of adverse effects were estimated by constructing a physiology-based pharmacokinetic model (PBPK), built with PK-Sim® software (Open Systems Pharmacology), using plasma concentration versus time data obtained from literature. Using the popPK model, it was possible to evaluate the efficacy of gentamicin for different minimum inhibitory concentrations and toxicity according to the dose administered. The PBPK model showed a high predictive performance, with a GMFE value of 1,13 for Cmax and 1,18 for AUC, meeting the double error criterion and was considered effective for predicting concentrations at different doses. Using this model, it was possible to simulate the concentration of gentamicin over a long period of time. The work thus proposed an approach aimed at optimizing dosages, according to the patient's clinical condition and bacterial infection, guaranteeing treatment efficacy and patient safety.