Optimal design for multiresponse pharmacokinetic-pharmacodynamic models - Dealing with unbalanced designs

Kayode Ogungbenro, Ivelina Gueorguieva, Oneeb Majid, Gordon Graham, Leon Aarons

    Research output: Contribution to journalArticlepeer-review


    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. © 2007 Springer Science+Business Media, LLC.
    Original languageEnglish
    Pages (from-to)313-331
    Number of pages18
    JournalJournal of pharmacokinetics and pharmacodynamics
    Issue number3
    Publication statusPublished - Jun 2007


    • D-optimality
    • Fixed effects
    • Mixed effects
    • Multiresponse
    • Nonlinear
    • Optimal design
    • Pharmacodynamics
    • Pharmacokinetics


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