Biomedical Applications of System Dynamics
Erik Mosekilde and Jakob Laugesen
Department of Physics
The Technical University of Denmark
2800 Lyngby, Denmark
Abstract
Systems Biology is one of the most exciting areas of science. Research in this field aims at
establishing a model-based description of the complex dynamic phenomena we observe in the living
world. The perspective is that a better understanding of the mechanisms and processes underlying the
regulation of the human body will improve the treatment of patients in the health care system, cut the
development costs of new drugs, and reduce the need for animal experiments. The modeling problems
we encounter in Systems Biology are similar in many respects to the problems addressed in
managerial or macroeconomic modeling, and there is a significant potential for using System
Dynamics in the biomedical field as well. The talk will present a particular example of work
performed in collaboration with Novo Nordisk and the Danish Medicines Agency.
The absorption kinetics of subcutaneously injected soluble insulin is unusual in that clinical
experiments show that a slow initial absorption after a couple of hours is replaced by a significantly
faster absorption. Moreover, experiments with different injection volumes and insulin concentrations
demonstrate that there is both a volume and a concentration effect. The slow initial phase disappears
if either the injected volume or the concentration of the injected insulin is reduced. On the other hand,
in the limits of very low concentrations or small volumes, a tail develops on the absorption curve,
representing a new type of slow process.
A System Dynamics model of this absorption scenario was original developed in collaboration with
the Steno Memorial Hospital in the mid 1980's [1]. In spite of the fact that the insulin concentrations
in the mean time have increased by an order of magnitude, the model continues to correctly predict
the absorption curves, and we are presently developing variants of the model that can explain the
absorption curves for other insulin forms, some of which are bound to protein as they are injected or
bind to protein as they enter the blood vessels while yet others are injected in crystalline form or
precipitate immediately after the injection. A particularly interesting aspect is the sensitivity of the
absorption rate to variations of the blood perfusion at the injection site.
[1] E. Mosekilde, K.S. Jensen, C. Binder, S. Pramming and B. Thorsteinsson: 'Modeling absorption
kinetics of subcutaneously injected soluble insulin’, J. Pharmacokin. Biopharm. 17, 67-87 (1989).
(First presented at the Int. Systems Dynamics Conf., Oslo 1984).
