Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus

• DOI: 10.1007/s00228-011-1207-0
• Publication Date: 2012-01-24T13:02:33Z
• Authors: Christophe Bardin; Estelle Nobecourt; Etienne Larger; François Chast; Jean-Marc Treluyer; Saik Urien
• Keywords: Adult; Aged, 80 and over; Male; 2. Zero hunger; Body Weight; Middle Aged; Metformin; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Diabetes Mellitus, Type 2; Nonlinear Dynamics; Humans; Hypoglycemic Agents; Female; Obesity; Aged

The objective of this study was to develop a population pharmacokinetic model and investigate the effect of several demographic covariates on metformin pharmacokinetics in patients with type 2 diabetes mellitus, over a wide range of weights.A total of 105 patients received different metformin regimens, and pharmacokinetic sampling included a minimum of two concentrations per patient. Plasma determination of metformin was assayed by high performance liquid chromatography. Population pharmacokinetics was modelled using a nonlinear mixed effects model program (Monolix version 3.1 s).An open one-compartment model adequately described metformin data. Lean body weight was a better size descriptor than actual body weight or ideal body weight for clearance (CL/F) and volume (V/F) parameters. CL/F was negatively related to age and serum creatinine (SCr). The estimation of specific coefficients for these effects gave better results than the use of renal function descriptors (Cockroft or MDRD). A dose effect in the relative bioavailability was demonstrated.The pharmacokinetics of metformin was influenced by lean body weight on an allometric basis and was related to markers of renal function, age, and serum creatinine in this population of 105 patients.