Pharmacokinetic pharmacodynamic modeling and simulation methods applied to evaluation of therapeutic strategies

Are Evidence-Based Medicine and its associated search for standardization compatible with the patient intra- and interindividual variability in therapeutic response? Through three successive questions (1 – Is variability significant in infectious diseases ; 2 – Is it possible to describe and model this variability ; 3 - How can we apply this information to evaluate the usefulness of therapeutic strategies), we show that it does not seem possible to ignore this variability, and that pharmacokinetic-pharmacodynamic modeling can describe it adequately. This study also shows that many current treatment strategies do not take into account this variability sufficiently. These findings challenge the relevance of current practices in drug dosage regimens calculation, including the exclusive use of covariates, and underline the interest of therapeutic drug monitoring and individualized drug therapy