Optimal Design for Multiresponse Pharmacokinetic–Pharmacodynamic Models – Dealing with Unbalanced Designs

D-optimality Fixed effects Optimal design Blood Pressure Cardiovascular Agents Nonlinear Models, Biological 01 natural sciences 03 medical and health sciences Multiresponse 0302 clinical medicine Pharmacodynamics Nonlinear Dynamics Heart Rate Research Design Mixed effects Humans Computer Simulation Pharmacokinetics 0101 mathematics
DOI: 10.1007/s10928-006-9048-7 Publication Date: 2007-02-06T20:35:50Z
ABSTRACT
This paper addresses the problem of determining D-optimal designs for multiresponse pharmacokinetic-pharmacodynamic (PKPD) experiments where data on each response variable can be collected at different times. Most previous multiresponse model optimal design applications have considered the case where all response variables are measured at the same time points. However in practice it may not be possible to have all responses measured at the same sampling times. We propose an optimal design method to take into account the unbalanced nature of the problem. The method developed was applied to a PKPD problem that involved describing the time course of drug plasma concentrations, heart rate and mean arterial blood pressure for both a fixed effects and mixed effects regression model. Additionally a simulation study was carried out in NONMEM for one such population optimal design problem.
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