Fuzzy simulation of pharmacokinetic models: Case study of whole body physiologically based model of diazepam

Ivelina I. Gueorguieva, Ivan A. Nestorov, Malcolm Rowland

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The aim of the present study is to develop and implement a methodology that accounts for parameter variability and uncertainty in the presence of qualitative and semi-quantitative information (fuzzy simulations) as well as when some parameters are better quantitatively defined than others (fuzzy-probabilistic approach). The fuzzy simulations method consists of (i) representing parameter uncertainty and variability by fuzzy numbers and (ii) simulating predictions by solving the pharmacokinetic model. The fuzzy-probabilistic approach includes an additional transformation between fuzzy numbers and probability density functions. To illustrate the proposed method a diazepam WBPBPK model was used where the information for hepatic intrinsic clearance determined by in vitro-in vivo scaling was semi-quantitative. The predicted concentration time profiles were compared with those resulting from a Monte Carlo simulation. Fuzzy simulations can be used as an alternative to Monte Carlo simulation.
    Original languageEnglish
    Pages (from-to)185-213
    Number of pages28
    JournalJournal of pharmacokinetics and pharmacodynamics
    Volume31
    Issue number3
    DOIs
    Publication statusPublished - Jun 2004

    Keywords

    • diazepam
    • fuzzy simulation
    • fuzzy-probabilistic
    • Monte Carlo simulation
    • parameter estimation
    • prediction
    • uncertainty
    • variability
    • whole body physiologically based pharmacokinetic model

    Fingerprint

    Dive into the research topics of 'Fuzzy simulation of pharmacokinetic models: Case study of whole body physiologically based model of diazepam'. Together they form a unique fingerprint.

    Cite this