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

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...

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Bibliographic Details
Published in:Journal of mathematical biology 2004-06, Vol.48 (6), p.591-604
Main Authors: Tornøe, Christoffer Wenzel, Jacobsen, Judith L, Madsen, Henrik
Format: Article
Language:English
Subjects:
Adolescent
Adult
Area Under Curve
Blood Glucose - drug effects
Blood Glucose - metabolism
C-Reactive Protein - metabolism
Cross-Over Studies
Diabetes
Double-Blind Method
Glucose Clamp Technique - methods
Humans
Hyperglycemia
Insulin - analogs & derivatives
Insulin - blood
Insulin - pharmacokinetics
Insulin - pharmacology
Insulin Aspart
Insulin, Regular, Pork
Male
Models, Biological
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Summary: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.
ISSN:0303-6812
1432-1416
DOI:10.1007/s00285-003-0257-z