title: Curvature-adjusted optimal design of sampling times for the inference of pharmacokinetic compartment models.
abstract: In pharmacokinetics, compartment models are often used to describe the time course of blood concentration after the administration of a drug. In this article, we propose an optimal design criterion for precise estimation of parameters included in the compartment model and illustrate the non-sequential design of sampling times of blood drug concentration data in individual pharmacokinetics. The proposed optimal design criterion minimizes the determinant of the mean-squared error matrix of the parameter estimator that is quadratically approximated by the curvature array. Therefore, the proposed criterion considers the intrinsic and parameter-effects nonlinearity underlying the compartment model, and so is applicable in a pharmacokinetic experiment where the sample size of the blood drug concentration data is quite small.
authors.affiliation: Department of Drug Evaluation and Informatics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. daimon@u-shizuoka-ken.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Masashi
authors.initials: M
authors.lastname: Goto
mesh_terms: D001682:Biological Availability; D006801:Humans; D007564:Japan; D015233:Models, Statistical; D010599:Pharmacokinetics; D012107:Research Design / Q000706:statistics & numerical data*; D012494:Sampling Studies