An in-silico Analysis of the Ability of Dynamic Tests to Trace the Kinetic Behaviour of Insulin Sensitizer Drugs

Type of content
Conference Contributions - Published
Thesis discipline
Degree name
Publisher
University of Canterbury. Mechanical Engineering
Journal Title
Journal ISSN
Volume Title
Language
Date
2011
Authors
Docherty, P.D.
Chase, Geoff
Lotz, T.
Berkeley, J.
Shaw, Geoff
Abstract

A Monte Carlo analysis was undertaken to measure the ability of a series of dynamic insulin sensitivity and secretion tests (DISST) to observe and quantify the time-varying effect of an insulin sensitizer drug. Physiological parameter values from an insulin resistant individual were used to simulate a series of DISST tests with the effects a hypothetical sensitizer drug (based on Metformin) that was assumed to elevate insulin sensitivity (D) by 50%, and have absorption (Dk1) and decay (Dk2) half-lives of ~30 and ~140 minutes respectively. Noise was added to data sampled from the simulation and allowed repeated identification of pharmaco-kinetic/dynamic parameters in clinically realistic data. The coefficients of variation (CV) of the drug variables in this Monte Carlo analysis were CV-D=0.9%, CVDk1= 116.3%, and CV-Dk2=41.4% respectively. Although the CV values for the drug kinetic rates did not indicate considerable stability, the identified time-varying insulin sensitivity profile was relatively accurate to the simulation profile (median error of 0.047 L/mU/min (~2%) and IQR of -0.093 to 0.184 L/mU/min (-4% to 8%)). This result indicates that the proposed method for identifying drug parameters using a series of dynamic tests is able to capture the overall effect of the drug, but has a potentially limited ability to identify the drug parameters individually. Thus, the existing method of arduous, frequently-sampled steady-state tests for the measurement of drug pharmacokinetics and dynamics could be replaced with a series of sparsely-sampled dynamic tests.

Description
(invited)<br />
Citation
Docherty, P.D., Chase, J.G., Lotz, T., Berkeley, J., Shaw, G.M. (2011) An in-silico Analysis of the Ability of Dynamic Tests to Trace the Kinetic Behaviour of Insulin Sensitizer Drugs. Milan, Italy: 18th World Congress of the International Federation of Automatic Control 2011 (IFAC 2011), 28 Aug-2 Sep 2011. 6pp.
Keywords
physiological modeling, pharmacokinetics/dynamics, parameter-identification, insulin sensitivity
Ngā upoko tukutuku/Māori subject headings
ANZSRC fields of research
Fields of Research::32 - Biomedical and clinical sciences::3201 - Cardiovascular medicine and haematology::320102 - Haematology
Fields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320208 - Endocrinology
Field of Research::11 - Medical and Health Sciences::1101 - Medical Biochemistry and Metabolomics
Field of Research::01 - Mathematical Sciences
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