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

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.

Limited sampling strategy for determining metformin area under the plasma concentration–time curve

“…The LSS model was further validated using data from 16 previously published studies . The results (Table , Figure , Supplementary Figures S7 and S8) indicated that the AUC(0,24 h) predicted by the two point LSS model was in excellent agreement ( r 2 = 0.976, bias −1.0%, precision 4.3%) with the corresponding AUC(0,24 h) best estimates, over a wide range (3.8–22.4 μg h l −1 ) of AUC(0,24 h) values and under a variety of demographic, experimental and clinical conditions.…”

In silico diabetológia

“…A Sorensen-modellt a közelmúltban NIDDM-páciensekre is adaptálták [6]. Sun és mtsai a metformin részletes farmakokinetikai-farmakodinamikai (PK-PD) modelljéről számoltak be [7].…”

Evaluation of treatment regimens for blood glucose regulation in type II diabetes using pharmacokinetic-pharmacodynamic modeling

“…Metformin Due to multi-factorial mechanism of action of metformin, a multi-compartment PK-PD model of metformin for the treatment of type II diabetes mellitus is used as described in [9][10][11]. This model constitutes three compartments including the GI tract (gut), liver and periphery.…”

“…For the oral administration, the pharmacokinetics of metformin from mouth to the GI lumen is described by the following equation: (9) where α and β are rate constants; A and B represent the contribution of the corresponding exponentials. These parameters were estimated by optimization using experimental data points in [9].…”

“…These parameters were estimated by optimization using experimental data points in [9]. The transient changes of metformin amounts at different bio-phases can be obtained as indicated in equations 5-8.…”