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 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.
Tornøe
Christoffer Wenzel
CW
Informatics and Mathematical Modelling, Technical University of Denmark, Building 321, 2800 Lyngby, Denmark. christoffer.tornoe@ferring.com
Jacobsen
Judith L
JL
Madsen
Henrik
H
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D061267:Insulin Aspart; D061389:Insulin, Regular, Pork; D008297:Male; D008954:Models, Biological
D001786:Blood Glucose; D007328:Insulin; D061389:Insulin, Regular, Pork; D002097:C-Reactive Protein; C000006:insulin, neutral; D061267:Insulin Aspart