title: Optimization of human dose prediction by using quantitative and translational pharmacology in drug discovery.
abstract: In this perspective article, we explain how quantitative and translational pharmacology, when well-implemented, is believed to lead to improved clinical candidates and drug targets that are differentiated from current treatment options. Quantitative and translational pharmacology aims to build and continuously improve the quantitative relationship between drug exposure, target engagement, efficacy, safety and its interspecies relationship at every phase of drug discovery. Drug hunters should consider and apply these concepts to develop compounds with a higher probability of interrogating the clinical biological hypothesis. We offer different approaches to set an initial effective concentration or pharmacokinetic-pharmacodynamic target in man and to predict human pharmacokinetics that determine together the predicted human dose and dose schedule. All concepts are illustrated with ample literature examples.
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Tjerk
authors.initials: T
authors.lastname: Bueters
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gibson
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, Upper Gwynedd, PA 19446, USA.
authors.forename: Sandra A G
authors.initials: SA
authors.lastname: Visser
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations