RT Journal Article
SR Electronic
T1 Impact of Physiologically Based Pharmacokinetic Modeling and Simulation in Drug Development
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1994
OP 2003
DO 10.1124/dmd.113.052803
VO 41
IS 12
A1 Carole E. Shardlow
A1 Grant T. Generaux
A1 Aarti H. Patel
A1 Guoying Tai
A1 Thuy Tran
A1 Jackie C. Bloomer
YR 2013
UL http://dmd.aspetjournals.org/content/41/12/1994.abstract
AB Physiologically based pharmacokinetic modeling and simulation can be used to predict the pharmacokinetics of drugs in human populations and to explore the effects of varying physiologic parameters that result from aging, ethnicity, or disease. In addition, the effects of concomitant medications on drug exposure can be investigated; prediction of the magnitude of drug interactions can impact regulatory communications or internal decision-making regarding the requirement for a clinical drug interaction study. Modeling and simulation can also help to inform the design and timings of clinical drug interaction studies, resulting in more efficient use of limited resources and improved planning in addition to promoting mechanistic understanding of observed drug interactions. These approaches have been used in GlaxoSmithKline from drug discovery to registration and have been applied to 41 drugs from a number of therapeutic areas. This report highlights the variety of questions that can be addressed by prospective or retrospective application of modeling and simulation and the impact this can have on clinical drug development (from candidate selection through clinical development to regulatory submissions).