Open Access

ARTICLE

Mechanism Based Pharmacokinetic Pharmacodynamic Modeling of Vildagliptin as an Add-on to Metformin for Subjects with Type 2 Diabetes

Marziyeh Eftekhari¹, Omid Vahidi^1,*

1 School of Chemical, Petroleum and Gas Engineering, Iran University of Science and Technology, Narmak, Tehran, Iran.

* Corresponding author: Omid Vahidi. Email: .

Computer Modeling in Engineering & Sciences 2018, 114(2), 153-171. https://doi.org/10.3970/cmes.2018.114.153

Abstract

Various drugs are used to maintain normoglycemia in subjects with type 2 diabetes mellitus. The combination of the drugs from different classes in one single tablet may enhance the effectiveness of the anti-diabetic drugs. To investigate the impact of combining drugs on the glucose regulation of subjects with type 2 diabetes, we propose a pharmacokinetic/pharmacodynamics (PK/PD) mathematical modeling approach for a combination of metformin and vildagliptin drugs. In the proposed modeling approach, two separate PK models representing oral administration of metformin and vildagliptin for diabetic subjects are interconnected to a PD model comprising a detailed compartmental physiological model representing the regulatory effect of insulin, incretins and glucagon hormones on glucose concentration in a human body. The impact of doses of individual drugs and their combination on the blood glucose concentration of a group of type 2 diabetic subjects is investigated. It is indicated that while administration of individual drugs reduces the blood glucose levels, since they have separate mechanisms of action, combining them synergizes lowering the blood glucose levels.

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