title: Quantitative systems pharmacology: a promising approach for translational pharmacology.
abstract: Biopharmaceutical companies have increasingly been exploring Quantitative Systems Pharmacology (QSP) as a potential avenue to address current challenges in drug development. In this paper, we discuss the application of QSP modeling approaches to address challenges in the translational of preclinical findings to the clinic, a high risk area of drug development. Three cases have been highlighted with QSP models utilized to inform different questions in translational pharmacology. In the first, a mechanism based asthma model is used to evaluate efficacy and inform biomarker strategy for a novel bispecific antibody. In the second case study, a mitogen-activated protein kinase (MAPK) pathway signaling model is used to make translational predictions on clinical response and evaluate novel combination therapies. In the third case study, a physiologically based pharmacokinetic (PBPK) model it used to guide administration of oseltamivir in pediatric patients.
authors.affiliation: Development Sciences, Genentech, United States. Electronic address: gadkar.kapil@gene.com.
authors.forename: K
authors.initials: K
authors.lastname: Gadkar
authors.affiliation: Development Sciences, Genentech, United States.
authors.forename: D
authors.initials: D
authors.lastname: Kirouac
authors.affiliation: Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center Basel, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Parrott
authors.affiliation: Development Sciences, Genentech, United States.
authors.forename: S
authors.initials: S
authors.lastname: Ramanujan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D053139:Oseltamivir / Q000493:pharmacokinetics / Q000494:pharmacology; D010601:Pharmacology, Clinical / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D049490:Systems Biology; D057170:Translational Research, Biomedical
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases