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A 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 ðtÞ 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 of M/C averaging 7.0 times, a result in keeping with prior simultaneous C and urine M collection studies and exhibiting a rate of apparent volume growth of V d that achieved limiting constant values. A simulated constant average drug mass multidosing protocol exhibited increased V d and t 1=2 with elapsing time, effects that have been observed experimentally during same-dose multidosing. The GPC heavy-tailed models explained multiple documented phenomena that were unexplained with lighter-tailed models. Keywords Metformin Á Pharmacokinetics Á Mathematical modelling pdf Á Clearance Á Serum concentration Á Drug mass Á Loading dose regimen Abbreviations AUC Area under the curve C(t) Concentration (model) CDF Cumulative density function CI Confidence interval, default 95% C in ðtÞ Concentration, constant infusion CL Plasma or serum clearance C max Local peak concentration C obs ðtÞ Observed concentrations (vector) C SS Steady-state concentration, terminal C in ðtÞ CV% Coefficient of variation D Dose mass df Degrees of freedom DF(n) Fractional dose multiplier D R An acronym of dosing rate E1 Monoexponential c e Àk t E2 Biexponential ED n Exponential density of n terms E PAH Renal extraction fraction PAH GD Gamma distribution GM Geometric mean GPC Gamma Pareto distribution H-MRT Harmonic mean residence time Electronic supplementary material The online version of this article (