RESEARCH ARTICLE


Pharmacokinetic-Pharmacodynamic Modeling of Metformin for the Treatment of Type II Diabetes Mellitus



Lin Suna, b, **, Ezra Kwoka, *, Bhushan Gopalunia, Omid Vahidia
a Department of Chemical and Biological Engineering, University of British Columbia, 2360 East Mall Vancouver, BC, Canada, V6T 1Z3
b China University of Petroleum, Beijing, Box 260 Changping District, Beijing, 102249, China


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Creative Commons License
© Sun et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Chemical and Biological, Engineering, University of British Columbia, 2360 East Mall Vancouver, BC, V6T 1Z3, Canada; Tel: +1 604 8221346; Fax: +1 604 8226003; E-mail: ezra@chbe.ubc.ca
** Lin Sun is a post-doctoral fellow from China University of Petroleum, Beijing, PRC


Abstract

Metformin is an antihyperglycemic agent commonly used for the treatment of Type II diabetes mellitus. However, its effects on patients are derived usually from clinical experiments. In this study, a dynamic model of Type II diabetes mellitus with the treatment of metformin is proposed. The Type II diabetic model is a modification of an existing compartmental diabetic model. The dynamic simulation of the metformin effect for a Type II diabetic patient is based on the pharmacokinetic and pharmacodynamic relationship with a human body. The corresponding model parameters are estimated by optimization using clinical data from published reports. Then, the effect of metformin in both intravenous and oral administration on a Type II diabetes mellitus model are compared. The combination treatment of insulin infusion plus oral metformin is shown to be superior than the monotherapy with oral metformin only. These results are consistent with the clinical understanding of the use of metformin. For further work, the model can be analyzed for evaluating the treatment of diabetes mellitus with different pharmacological agents.

Keywords: Metformin, Modeling, Type II diabetes mellitus, Pharmacokinetic, Pharmacodynamic, Insulin..