Pharmacokinetics and dose proportionality of extended-release metformin following administration of 1000, 1500, 2000 and 2500 mg in healthy volunteers

Biopharm Drug Dispos. 2004 Sep;25(6):261-3. doi: 10.1002/bdd.407.

Abstract

The pharmacokinetics and dose-exposure relationship of an extended-release formulation of metformin (ER-metformin) was investigated in a randomized, single-dose, four-period crossover study in 24 healthy male volunteers. During each study period, subjects received a randomly assigned dose containing 1000, 1500, 2000 or 2500 mg metformin. Blood samples were drawn 0-72 h after dosing for pharmacokinetic and dose-proportionality assessment. Although several pairwise comparisons between dose groups were significant (p<0.05) with respect to dose-normalized C(max), AUC(0-72 h), and AUC( infinity ), the magnitude of the difference across the dose range was <20% for AUC(0-72 h) and AUC( infinity ), and was < or = 30% for C(max). The results indicate a consistent and predictable increase in metformin exposure with an extended-release formulation of metformin over 1000 to 2500 mg.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Metformin / administration & dosage*
  • Metformin / blood
  • Metformin / pharmacokinetics*

Substances

  • Delayed-Action Preparations
  • Hypoglycemic Agents
  • Metformin