Lactulose, 51Cr-labelled ethylenediaminetetra-acetate, L-rhamnose and polyethyleneglycol 400 [corrected] as probe markers for assessment in vivo of human intestinal permeability

Clin Sci (Lond). 1986 Jul;71(1):71-80. doi: 10.1042/cs0710071.


The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), L-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for L-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of L-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress. The 5 h permeation of lactulose, but not of L-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P less than 0.001). These findings are compatible with three distinct pathways of unmediated mucosal permeation, L-rhamnose (radius less than 0.4 nm) passing mainly through small aqueous 'pores' of high incidence, lactulose and 51Cr-EDTA (radius greater than 0.5 nm) through larger aqueous 'channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous 'pores'.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Cell Membrane Permeability / drug effects
  • Cetrimonium Compounds / pharmacology
  • Chromium Radioisotopes
  • Disaccharides / metabolism*
  • Edetic Acid / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Lactulose / metabolism*
  • Osmolar Concentration
  • Polyethylene Glycols / metabolism*
  • Rhamnose / metabolism*


  • Cetrimonium Compounds
  • Chromium Radioisotopes
  • Disaccharides
  • Polyethylene Glycols
  • Lactulose
  • Edetic Acid
  • Rhamnose