The integration of pharmacokinetics and pharmacodynamics: Understanding dose-response

Pharmacokinetic (PK) and pharmacodynamic (PD) studies have proven to be powerful and instructive tools, particularly in elucidating important aspects of human pharmacology. Nevertheless, they remain imperfect tools in that they only allow researchers to indirectly extrapolate, through computational modeling, the dynamic processes of drug action. Furthermore, neither tool alone provides a complete nor necessarily relevant picture of drug action. This review explores the utility and applications of PK and PD in the study of drugs, provides examples of lessons learned from their application to studies of human pharmacology, points out some of their limitations, and advances the thesis that these tools ideally should be employed together in an integrated approach. As we continue to apply these tools across the continuum of age and disease, they provide a powerful means to enhance our understanding of drug action, drug interactions, and intrinsic host factors that influence pharmacologic response.