The use of population modeling to optimize dosing of drugs used in anaesthesiology and intensive care

Effective pharmacotherapy requires an adequate drug dose that maximizes the effectiveness of therapy while minimizing adverse effects. Difficulties in dose selection arise from interindividual differences in drug pharmacokinetics and pharmacodynamics. Population modeling describes pharmacokinetic and pharmacodynamic processes in a population, taking into account the relationships in each patient, differences between patients, and the influence of covariates on drug pharmacokinetics and pharmacodynamics. The aim of this study was to develop population models for drugs used in anesthesiology and intensive care in special patient populations. The pharmacokinetics of sufentanil was described in infants and children after epidural and intravenous administration. The estimated absorption rate constant from the epidural space suggests slow systemic absorption of sufentanil and the possibility of flip-flop kinetics, which results in a slower decline in plasma concentrations at the end of drug administration compared with intravenous administration. The dependence of metabolic clearance on body weight and age was also demonstrated. A population model for the pharmacokinetics of tigecycline was developed for patients with sepsis or septic shock. No relationship between pharmacokinetic parameters and patient characteristics was detected, and the estimated interindividual and inter-occasion variability for clearance was small. This suggests that a universal dose is sufficient to achieve homogeneous drug exposure in critically ill patients. The pharmacokinetics of caspofungin was described in critically ill patients. The clearance and volume of central compartment showed systematic increase over time that was not explained by the covariates. The estimated increase in clearance values for three consecutive doses results in a clinically relevant reduction in drug exposure. The developed population models extend the knowledge of the pharmacokinetics of sufentanyl, tigecycline, and caspofungin. Simulations based on these models can aid the dosing decision-making process.