title: Modelling the dose-response relationship: the fair share of pharmacokinetic and pharmacodynamic information.
abstract: The aim of this paper is to investigate the role of drug concentration samplings in the modelling of the dose-response relationship.
  
  
  
  Using an initial PK/PD model, a reference dataset was simulated. PK and PD samples were extracted to create reduced datasets. PK/PD and K-PD models were fitted to theses reduced datasets. Post hoc estimates from both types of models were compared to the initial PK/PD model and performance was assessed.
  
  
  
  K-PD models were largely biased when the drug has a nonlinear elimination. PK/PD models with 1 PK and 2 PD samples were superior to K-PD models with 3 PD samples. PK/PD models with 1 or 2 PK samples and 3 PD samples proved to be superior to K-PD models with 4 PD samples.
  
  
  
  K-PD models should not be used when the drug has nonlinear elimination. K-PD models should not replace PK/PD modelling but are an alternative approach if the PD information is large enough.
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Canada.|Inventiv Health Clinical, Montréal, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: González-Sales
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Canada.|Centre de Recherches Mathématiques (CRM), Université de Montréal, Montréal, Canada.
authors.forename: Fahima
authors.initials: F
authors.lastname: Nekka
authors.affiliation: Inventiv Health Clinical, Montréal, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Tanguay
authors.affiliation: Inventiv Health Clinical, Montréal, Canada.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Tremblay
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Canada.|Centre de Recherches Mathématiques (CRM), Université de Montréal, Montréal, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000465:Algorithms; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D010599:Pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D012984:Software
keywords: K-PD; NONMEM®; PK/PD; dose-response relationship