Comparison of the gamma-Pareto convolution with conventional methods of characterising metformin pharmacokinetics in dogs

AbstractA model was developed for long term metformin tissue retention based upon temporally inclusive models of serum/plasma concentration (\( C \)) having power function tails called the gamma-Pareto type I convolution (GPC) model and was contrasted with biexponential (E2) and noncompartmental (NC) metformin models. GPC models of\( C \) have a peripheral venous first arrival of drug-times parameter, early\( C \) peaks and very slow washouts of\( C \). The GPC, E2 and NC models were applied to a total of 148 serum samples drawn from 20 min to 72 h following bolus intravenous metformin in seven healthy mongrel dogs. The GPC model was used to calculate area under the curve (AUC), clearance (\( CL \)), and functions of time,f(t), for drug mass remaining (M), apparent volume of distribution (\(V_{d}\)), as well as\(t_{1/2}\ f(t)\) for\( C \),\( M \) and\(V_{d}\). The GPC models of\( C \) yielded metformin\( CL \)-values that were 84.8% of total renal plasma flow (RPF) as estimated from meta-analysis. The GPC\( CL \)-values were significantly less than the corresponding NC and E2\( CL \)-values of 104.7% and 123.7% of RPF, respectively. The GPC plasma/serum only model predicted 78.9% drug\( M \) average urinary recovery at 72 h; similar to prior human urine drug\( M \) collection results. The GPC model\(t_{1/2}\) of\( M \),\( C \) and\(V_d\), were asymptotically proportional to elapsed time, with a constant limiting\(t_{1/2}\) ratio ofM/C averaging 7.0 times, a result in keeping ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research