title: Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacy-Pharmacology-Toxicology Department, Hôtel-Dieu, 1 Place du Parvis Notre-Dame, Paris Cédex 04, France. christophe.bardin@htd.aphp.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Bardin
authors.forename: Estelle
authors.initials: E
authors.lastname: Nobecourt
authors.forename: Etienne
authors.initials: E
authors.lastname: Larger
authors.forename: François
authors.initials: F
authors.lastname: Chast
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D017711:Nonlinear Dynamics; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin