CPSA Shanghai 2011
Changing Paradigm in Drug Discovery & Development:
East Meets West
April 13 - 16, 2011
Renaissance Shanghai Pudong Hotel
Shanghai, China
Abstract
Friday PM - Parallel Session III
Empirical, Mechanistic, or System? – The myths of PK/PD Modeling Approaches
Jenny Zheng, Pfizer
Classical pharmacokinetics (PK) is described as “what the body does to the drug” whereas classical pharmacodynamics (PD) is assessed as “what the drug does to the body”. PK/PD modeling is a technique that combines these two classic pharmacologic disciplines and integrates into one set of mathematical expressions that allows the quantitative description of the time course of relationship between concentration (dose) and effect intensity in response to a drug at a dose administered. Since the concept first established decades ago, PK/PD modeling and simulation has been widely used in prediction of efficacy outcomes in both preclinical and clinical setting. The PK/PD modeling technique field has also evolved from an empirical dose/concentration response model for numerous direct and reversibly acting drugs to a quantitative mechanistic target-mediated drug disposition model for monoclonal antibody and to recent emerging system biology approach which study the complicated interactions among the components of biological network at molecular level. The increasing complexity of models has become practically feasible primarily resulted from improved analytical methodologies (the ability of measurement of various biomarkers), advances in computer hardwares and softwares (allows to solve complicated mathematic models time-efficiently). Nowadays, reported data has shown that these diversified model approaches have significantly enhanced the confidence in predicting PK and efficacy outcomes for clinical candidates, thus reducing attrition in drug R&D process. In this presentation, the applications of the classic approach (empirical model) as well as contemporary modeling trend (mechanism-based, system-based) will be discussed. Their respective advantages and disadvantages will be highlighted as well.