Grey-box modelling of pharmacokinetic/pharmacodynamic systems

Christoffer Wenzel Tornøe, Judith L Jacobsen, Oluf Pedersen, Torben Hansen, Henrik Tækker Madsen

21 Citations (Scopus)

Abstract

Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling consists of using stochastic differential equations (SDEs) where the stochastic term in the differential equations represents unknown or incorrectly modelled dynamics of the system. The methodology behind the grey-box PK/PD modelling framework for systematic model improvement is illustrated using simulated data and furthermore applied to Bergman's minimal model of glucose kinetics using clinical data from an intravenous glucose tolerance test (IVGTT). The grey-box estimates of the stochastic system noise parameters indicate that the glucose minimal model is too simple and should preferably be revised in order to describe the complicated in vivo system of insulin and glucose following an IVGTT.
Original languageEnglish
JournalJournal of Pharmacokinetics and Pharmacodynamics
Volume31
Issue number5
Pages (from-to)401-17
Number of pages17
ISSN1567-567X
Publication statusPublished - 2004

Keywords

  • Blood Glucose
  • Glucose Tolerance Test
  • Humans
  • Insulin
  • Models, Biological
  • Stochastic Processes

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