A subcutaneous insulin pharmacokinetic model for computer simulation in a diabetes decision support role: model structure and parameter identification.
OBJECTIVE
The goal of this study was to develop a unified physiological subcutaneous (SC) insulin absorption model for computer simulation in a clinical diabetes decision support role. The model must model the plasma insulin appearance of a wide range of current insulins, especially monomer insulin and insulin glargine, utilizing common chemical states and transport rates, where appropriate.


METHODS
A compartmental model was developed with 13 patient-specific model parameters covering six diverse insulin types [rapid-acting, regular, neutral protamine Hagedorn (NPH), lente, ultralente, and glargine insulin]. Model parameters were identified using 37 sets of mean plasma insulin time-course data from an extensive literature review via nonlinear optimization methods.


RESULTS
All fitted parameters have a coefficient of variation <100% (median 51.3%, 95th percentile 3.6-60.6%) and can be considered a posteriori identifiable.


CONCLUSIONS
A model is presented to describe SC injected insulin appearance in plasma in a diabetes decision support role. Clinically current insulin types (monomeric insulin, regular insulin, NPH, insulin, and glargine) and older insulin types (lente and ultralente) are included in a unified framework that accounts for nonlinear concentration and dose dependency. Future work requires clinical validation using published pharmacokinetic studies.
Wong
Jason
J
Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand. xww10@student.canterbury.ac.nz
Chase
J Geoffrey
JG
Hann
Christopher E
CE
Shaw
Geoffrey M
GM
Lotz
Thomas F
TF
Lin
Jessica
J
Le Compte
Aaron J
AJ