Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide

Pharmacol Rep. 2010 Sep-Oct;62(5):956-65. doi: 10.1016/s1734-1140(10)70357-1.


Recently, it has been reported that metformin may attenuate inflammation and directly act on the central nervous system. Using the HPLC method, in Wistar rats, we assessed the changes in metformin concentrations in various brain regions (pituitary gland, olfactory bulb, hypothalamus, cerebellum, hippocampus, striatum, frontal cortex), cerebrospinal fluid and plasma after single and chronic oral administration, in the model of systemic inflammation induced by lipopolysaccharide (ip). Regarding the influence of systemic inflammation on metformin distribution, the pituitary gland demonstrated the highest its level after single and chronic administration (28.8 ± 3.5 nmol/g and 24.9 ± 3.2 nmol/g, respectively). We concluded that orally-dosed metformin rapidly crosses the blood-brain barrier and differently accumulates in structures of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / cerebrospinal fluid
  • Hypoglycemic Agents / pharmacokinetics*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Metformin / blood
  • Metformin / cerebrospinal fluid
  • Metformin / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Tissue Distribution


  • Hypoglycemic Agents
  • Lipopolysaccharides
  • Metformin