Pharmacokinetics/Pharmacodynamics and the Stages of Drug Development: Role of Modeling and Simulation

Overview

Journal AAPS J

Specialty Pharmacology

Date 2005 Dec 16

PMID 16353932

Citations 53

Authors

Jenny Y Chien

Stuart Friedrich

Michael A Heathman

Dinesh P De Alwis

Vikram Sinha

Affiliations

Soon will be listed here.

Abstract

Pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation (M&S) are well-recognized powerful tools that enable effective implementation of the learn-and-confirm paradigm in drug development. The impact of PK/PD M&S on decision making and drug development risk management is dependent on the question being asked and on the availability and quality of data accessible at a particular stage of drug development. For instance, M&S methodologies can be used to capture uncertainty and use the expected variability in PK/PD data generated in preclinical species for projection of the plausible range of clinical dose; clinical trial simulation can be used to forecast the probability of achieving a target response in patients based on information obtained in early phases of development. Framing the right question and capturing the key assumptions are critical components of the "learn-and-confirm" paradigm in the drug development process and are essential to delivering high-value PK/PD M&S results. Selected works of PK/PD modeling and simulation from preclinical to phase III are presented as case examples in this article.

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