title: Optimizing the in vitro and clinical assessment of drug interaction risk by understanding co-medications in patient populations.
abstract: BACKGROUND
  Pharmacokinetic drug interactions resulting from the inhibition of drug elimination mechanisms are of concern in drug development due to the clinical risk associated with elevated drug concentrations. Advances in understanding the mechanistic basis of these drug interactions has resulted in the widespread application of mechanistic in vitro assays and the conduct of clinical drug interaction studies to predict and quantify the risks in drug development.
  
  
  METHODS
  The authors investigate co-medication prescriptions in target patient populations and characterize the mechanistic basis and clinical impact of known co-medication drug interactions. This has enabled identification of critical mechanistic in vitro studies and provided options to manage co-medication use in clinical studies. Furthermore, they demonstrate, for the pharmaceutical scientist, how improved understanding of the drug interactions risks associated with key medications in a target therapeutic area, can help prioritize the conduct of in vitro data and optimize the timing of the clinical drug interaction studies required to characterize drug interaction risks.
  
  
  CONCLUSIONS
  This approach provides a more targeted strategy to drug interaction data generation, as routine application of assays may provide limited impact on drug progression decisions. Assessing co-medications in the target patient population enables early discharge of the safety risks associated with drug interactions and reduced investment in drug interaction studies.
authors.affiliation: Drug Metabolism and Pharmacokinetics, GlaxoSmithKline R&D, Park Rd, Ware, Herts, SG12 0DP, UK. Jackie.C.Bloomer@gsk.com
authors.forename: Jackie
authors.initials: J
authors.lastname: Bloomer
authors.forename: Geo
authors.initials: G
authors.lastname: Derimanov
authors.forename: Etienne
authors.initials: E
authors.lastname: Dumont
authors.forename: Harma
authors.initials: H
authors.lastname: Ellens
authors.forename: Christopher
authors.initials: C
authors.lastname: Matheny
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods; D003657:Decision Making; D015195:Drug Design; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010599:Pharmacokinetics; D012306:Risk
chemical_list: D004364:Pharmaceutical Preparations