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

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dc.contributor.authorDocherty, P.D.
dc.contributor.authorChase, Geoff
dc.contributor.authorLotz, T.
dc.contributor.authorBerkeley, J.
dc.contributor.authorShaw, Geoff
dc.date.accessioned2012-02-13T20:40:52Z
dc.date.available2012-02-13T20:40:52Z
dc.date.issued2011en
dc.description(invited)<br />en
dc.description.abstractA 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.en
dc.identifier.citationDocherty, 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.en
dc.identifier.doihttps://doi.org/10.3182/20110828-6-IT-1002.01687
dc.identifier.urihttp://hdl.handle.net/10092/6298
dc.language.isoen
dc.publisherUniversity of Canterbury. Mechanical Engineeringen
dc.rights.urihttps://hdl.handle.net/10092/17651en
dc.subjectphysiological modelingen
dc.subjectpharmacokinetics/dynamicsen
dc.subjectparameter-identificationen
dc.subjectinsulin sensitivityen
dc.subject.anzsrcFields of Research::32 - Biomedical and clinical sciences::3201 - Cardiovascular medicine and haematology::320102 - Haematologyen
dc.subject.anzsrcFields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320208 - Endocrinologyen
dc.subject.anzsrcField of Research::11 - Medical and Health Sciences::1101 - Medical Biochemistry and Metabolomicsen
dc.subject.anzsrcField of Research::01 - Mathematical Sciencesen
dc.titleAn in-silico Analysis of the Ability of Dynamic Tests to Trace the Kinetic Behaviour of Insulin Sensitizer Drugsen
dc.typeConference Contributions - Published
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