title: Grey-box pharmacokinetic/pharmacodynamic modelling of a euglycaemic clamp study.
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.
authors.affiliation: Informatics and Mathematical Modelling, Technical University of Denmark, Building 321, 2800 Lyngby, Denmark. christoffer.tornoe@ferring.com
authors.forename: Christoffer Wenzel
authors.initials: CW
authors.lastname: Tornøe
authors.forename: Judith L
authors.initials: JL
authors.lastname: Jacobsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Madsen
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007328:Insulin; D061389:Insulin, Regular, Pork; D002097:C-Reactive Protein; C000006:insulin, neutral; D061267:Insulin Aspart