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

Purpose: 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 differe...

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Publicado en:European Journal of Clinical Pharmacology Vol. 68; no. 6; pp. 961 - 969
Autores principales: Bardin, Christophe, Nobecourt, Estelle, Larger, Etienne, Chast, François, Treluyer, Jean-Marc, Urien, Saik
Formato: equations & formulas research tables/charts Journal Article
Publicado: Springer Nature Jun2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2012
      vid: 68
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      pub: Springer Nature
      place: New York, New York
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        atl: Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus.
      aug:
        au:
          Bardin, Christophe
          Nobecourt, Estelle
          Larger, Etienne
          Chast, François
          Treluyer, Jean-Marc
          Urien, Saik
        affil: Pharmacy-Pharmacology-Toxicology Department, Hôtel-Dieu, AP-HP, 1, Place du Parvis Notre-Dame 75181 Paris Cédex 04 France
      sug:
        subj:
          Diabetes Mellitus, Type 2 Drug Therapy
          Metformin Administration and Dosage
          Metformin Pharmacokinetics
          Human
          Models, Statistical
          Obesity
          Body Weight
          Chromatography, High Pressure Liquid
          Metformin Blood
          Fat Free Mass
          Metabolic Clearance Rate
          Biological Availability
          Creatinine Blood
          Age Factors
          Kidney
          Male
          Female
          Biological Assay
          Data Analysis Software
          Descriptive Statistics
          Adult
          Middle Age
          Aged
          Aged, 80 and Over
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Aged, 80 & over
          Male
          Female
      ab: Purpose: 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. Conclusion: 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.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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