Pharmacokinetic and Pharmacodynamic Modeling

Abstract

Pharmacokinetic and pharmacodynamic (PKPD) concepts and approaches play a critical role by increasing the efficiency throughout the drug development process and optimizing clinical therapeutics. Innovative quantitative analysis that integrate PKPD and disease progression knowledge are pivotal in regulatory decision-making and have shown to provide supportive evidence of effectiveness. Objective approaches to dose-selection that are informed by exposure-response analyses can assist in visualizing benefit-risk profiles on an individual and population level. Clinical trial simulations using quantitative models that incorporate structural and stochastic components along with prior knowledge can allow for informing clinical trial design features, dose selection in unstudied patient populations, and regulatory policy development. This chapter presents various PKPD-based analyses throughout the drug development process and within precision medicine. Emphasis on the use of PKPD analysis for proof of concept, dose-ranging, and first in human dose studies are subsequently provided. Case studies are highlighted to better illustrate the impact of quantitative analyses for decision-making.