title: Pharmacokinetics/Pharmacodynamics and the stages of drug development: role of modeling and simulation.
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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285, USA. jchien@lilly.com
authors.forename: Jenny Y
authors.initials: JY
authors.lastname: Chien
authors.forename: Stuart
authors.initials: S
authors.lastname: Friedrich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heathman
authors.forename: Dinesh P
authors.initials: DP
authors.lastname: de Alwis
authors.forename: Vikram
authors.initials: V
authors.lastname: Sinha
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003198:Computer Simulation / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000706:statistics & numerical data