Approaches for dosage individualisation in critically ill patients

Introduction: Pharmacokinetic variability in critically ill patients is the result of the overlapping of multiple pathophysiological and clinical factors. Unpredictable exposure from standard dosage regimens may influence the outcome of treatment. Therefore, strategies for dosage individualisation are recommended in this setting. Areas covered: The authors focus on several approaches for dosage individualisation that have been developed, ranging from the well-established therapeutic drug monitoring (TDM) up to the innovative application of pharmacogenomics criteria. Furthermore, the authors summarise the specific population pharmacokinetic models for different drugs developed for critically ill patients to improve the initial dosage selection and the Bayesian forecasting of serum concentrations. The authors also consider the use of Monte Carlo simulation for the selection of dosage strategies. Expert opinion: Pharmacokinetic/pharmacodynamics (PK/PD) modelling and dosage individualisation methods based on mathematical and statistical criteria will contribute in improving pharmacologic treatment in critically ill patients. Moreover, substantial effort will be necessary to integrate pharmacogenomics criteria into critical care practice. The lack of availability of target biomarkers for dosage adjustment emphasizes the value of TDM which allows a large part of treatment outcome variability to be controlled.