title: A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies.
abstract: Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.
authors.affiliation: School of Pharmacy, University of Otago, Frederick St, Dunedin, Otago 9001, New Zealand. lfandfl@gmail.com
authors.forename: Lee Kien
authors.initials: LK
authors.lastname: Foo
authors.forename: James
authors.initials: J
authors.lastname: McGree
authors.forename: Stephen
authors.initials: S
authors.lastname: Duffull
mesh_terms: D001800:Blood Specimen Collection / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D017711:Nonlinear Dynamics; D004364:Pharmaceutical Preparations / Q000097:blood; D010599:Pharmacokinetics; D012107:Research Design; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations