Title:Integration of Pharmacogenomics and Pharmacometrics to Support Drug Development, Regulatory and Therapeutic Decisions
VOLUME: 12 ISSUE: 1
Author(s):Mukul Minocha, Sagar Shukla and Jogarao Gobburu
Affiliation:Center for Translational Medicine, University of Maryland Baltimore, School of Pharmacy, 20N Pine Street, Baltimore, 21021, USA.
Keywords:Clinical-trial, modeling and simulation, drug-development, pharmacokinetics, pharmacodynamics, pharmacometrics,
pharmacogenetics.
Abstract:Pharmacogenomics as a science aims at individualizing the treatment based on the genetic makeup, to mitigate
the chances of adverse drug events and/or to maximize the efficacy in a sub-population. Pharmacometrics is the science of
quantifying disease, drug and trial characteristics with the goal to influence key drug development, regulatory and therapeutic
decisions. Pharmacometric analysis as a tool has revolutionized the way dose/dosing regimens or clinical trials are
being designed prospectively to answer key drug development questions. Exposure-response relationships established in
adult patients have made it possible to make dosing recommendations in special populations (pediatrics and organ function
impaired patients), leading to approval of doses/dosing regimen that were not studied in registration trials. Until now,
pharmacogenomics is predominantly used retrospectively to understand the between subject variability of drug’s pharmacokinetic
and pharmacodynamic properties. In this article we discuss how the advent of advanced pharmacometric tools
can leverage prior pharmacogenomic information to prospectively design late stage clinical trials. In addition, selected
case studies are presented that demonstrates the application of modeling and simulation in supporting dose selection in patients
with allelic variants across different therapeutic areas.
