title: A question-based approach to adopting pharmacogenetics to understand risk for clinical variability in pharmacokinetics in early drug development.
abstract: Understanding genetic variations that influence pharmacokinetics (PK) in humans is important for optimal clinical use of drugs. Guidances for making decisions on when to conduct pharmacogenetic research during drug development have been proposed by regulatory agencies, but their uniform adoption presents problems due to an inherent lack of flexibility. A questions-based approach (QBA) was developed to enable drug development teams at Merck to iteratively and flexibly evaluate the potential impact of pharmacogenetics (PGx) on clinical pharmacokinetic variability.
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey, USA.
authors.forename: R
authors.initials: R
authors.lastname: Evers
authors.affiliation: Clinical Pharmacogenomics, Merck & Co, North Wales, Pennsylvania, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Blanchard
authors.affiliation: 1] Clinical Pharmacogenomics, Merck & Co, North Wales, Pennsylvania, USA [2] Current affiliation: Gentris Corporation, Morrisville, North Carolina, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Warner
authors.affiliation: Clinical Pharmacology, Merck & Co., North Wales, Pennsylvania, USA.
authors.forename: D
authors.initials: D
authors.lastname: Cutler
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., West Point, Pennsylvania, USA.
authors.forename: N G B
authors.initials: NG
authors.lastname: Agrawal
authors.affiliation: Clinical Pharmacogenomics, Merck & Co., West Point, Pennsylvania, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Shaw
mesh_terms: D000465:Algorithms; D000818:Animals; D001692:Biological Transport / Q000235:genetics*; D001711:Biotransformation / Q000235:genetics*; D055808:Drug Discovery / Q000379:methods*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D010641:Phenotype; D018570:Risk Assessment