Grey-box pharmacokinetic/pharmacodynamic modelling of a euglycaemic clamp study

Christoffer Wenzel Tornøe, Judith L. Jacobsen, Henrik Madsen

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    Abstract

    Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling the pharmacokinetics and pharmacodynamics of the in vivo system of insulin and glucose and to estimate model and derived PK/PD parameters. The concept behind grey-box modelling consists in using a priori physiological knowledge along with information from data in the estimation of model parameters. The PK/PD properties of two types of insulin are investigated in a euglycaemic clamp study where a single bolus of insulin is injected subcutaneously. The effect of insulin on the glucose disappearance is investigated by artificially maintaining a blood glucose concentration close to the normal fasting level. The infused glucose needed to maintain the clamped blood glucose concentration can therefore be used as a measure for the glucose utilization. The PK and PD parameters are successfully estimated simultaneously thereby describing the uptake, distribution, and effect of the two different types of insulin.
    Original languageEnglish
    JournalJournal of Mathematical Biology
    Volume48
    Issue number6
    Pages (from-to)591-604
    ISSN0303-6812
    DOIs
    Publication statusPublished - 2004

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