Effect of anionic macromolecules on intestinal permeability of furosemide

Drug Dev Ind Pharm. 2015 Feb;41(2):190-3. doi: 10.3109/03639045.2013.851210. Epub 2013 Nov 6.

Abstract

Context: Furosemide is an anionic molecule and has very low absorption in gastro intestinal tract.

Objective: The aim of this study was to investigate the effect of anionic macromolecules on the intestinal permeability of Furosemide.

Materials and methods: The intestinal permeability of Furosemide was determined using single-pass intestinal perfusion technique in rats. Briefly a jejunal segment of ∼10 cm was isolated and cannulated in both ends for inlet and outlet solution. The perfusate was collected every 10 min and samples were analyzed using the RP-HPLC method. Test samples containing furosemide and two anionic macromolecules, sodium carboxy methyl cellulose and sodium alginate, at different concentrations were used.

Results: The obtained data showed that existence of Sodium carboxy methyl cellulose significantly increased the Peff values in all three investigated concentrations (p < 0.05) but sodium alginate only in concentrations <0.1% increased drug permeability.

Discussion: It is concluded that the anionic macromolecules at specific concentrations could alter the permeability of anionic drugs across the biological membranes.

Conclusions: Donnan phenomenon and chelating property of macromolecules could be attributed to the observed effect.

Keywords: Donnan effect; furosemide; single-pass intestinal perfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / administration & dosage
  • Alginates / chemistry
  • Animals
  • Anions
  • Carboxymethylcellulose Sodium / administration & dosage
  • Carboxymethylcellulose Sodium / chemistry
  • Diuretics / administration & dosage
  • Diuretics / pharmacokinetics
  • Furosemide / administration & dosage
  • Furosemide / pharmacokinetics*
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / chemistry
  • Intestinal Absorption
  • Jejunum / metabolism
  • Male
  • Perfusion
  • Permeability
  • Rats
  • Rats, Wistar
  • Viscosity

Substances

  • Alginates
  • Anions
  • Diuretics
  • Hexuronic Acids
  • Furosemide
  • Glucuronic Acid
  • Carboxymethylcellulose Sodium