The application of population pharmacokinetic modeling to individualized antibiotic therapy

Abstract

This paper describes applications of population pharmacokinetic modeling to the optimization of antibiotic dosing. Parametric and nonparametric pharmacokinetic modeling approaches are discussed. Population models can be important extensions of therapeutic drug monitoring (TDM) in infectious disease. The concept of population model-based individualized antimicrobial therapy is described. With the availability of population modeling for obtaining PK parameter estimates, the focus has shifted to quantifying the antimicrobial effect and linking kinetics to drug effects. Examples of integrated pharmacokinetic–pharmacodynamic (PK–PD) models to describe bacterial killing as a function of drug concentration are discussed. Application of PK–PD mathematical models that correlate with microbiological and clinical outcomes will provide us with a better rationale for the proper dose selection of anti-infective therapy in different patient populations.