title: Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: a hypothesis.
abstract: OBJECTIVE
  Clinical interpretation of urinary recovery ratios of lactulose and mannitol is hampered by incomplete understanding of the mechanisms of transmucosal passage. The aim of this study was to compare in vivo and in vitro probe permeability.
  
  
  METHODS
  Stripped sheets of small intestine from rodents and human biopsy specimens were mounted in Ussing chambers, and mucosa-to-serosa fluxes of lactulose and mannitol were determined. Urinary recovery of orally applied probes was measured in rodents, cats, and humans.
  
  
  RESULTS
  In vitro lactulose/mannitol flux ratios were close to 0.8 in all species. Urinary recovery ratios differed between rodents and cats or humans; low ratios in cats and humans were due to high mannitol recovery.
  
  
  CONCLUSIONS
  Interspecies variation in urinary recovery of mannitol is caused by differences specific for the intact small intestines in vivo. Because hyperosmolality of villus tips in vivo varies, being highest in humans and cats as a result of vascular countercurrent multiplication, it is hypothesized that the high urinary recovery of mannitol in these species is caused by solvent drag through pores that allow the passage of mannitol but not of lactulose. Therefore, the lactulose/mannitol ratio is primarily a standard for the normal functioning of villus epithelial cells in metabolite absorption and for normal villus blood flow.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P B
authors.initials: PB
authors.lastname: Bijlsma
authors.forename: R A
authors.initials: RA
authors.lastname: Peeters
authors.forename: J A
authors.initials: JA
authors.lastname: Groot
authors.forename: P R
authors.initials: PR
authors.lastname: Dekker
authors.forename: J A
authors.initials: JA
authors.lastname: Taminiau
authors.forename: R
authors.initials: R
authors.lastname: Van Der Meer
mesh_terms: D000818:Animals; D004492:Edetic Acid / Q000493:pharmacokinetics; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D007792:Lactulose / Q000493:pharmacokinetics* / Q000652:urine; D008353:Mannitol / Q000493:pharmacokinetics* / Q000652:urine; D008954:Models, Biological; D009997:Osmotic Pressure; D010539:Permeability; D011817:Rabbits; D051381:Rats; D012996:Solutions / Q000494:pharmacology
chemical_list: D012996:Solutions; D008353:Mannitol; D007792:Lactulose; D004492:Edetic Acid; D006735:Horseradish Peroxidase