Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: A hypothesis

Background/Aims : 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...

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 1995-03, Vol.108 (3), p.687-696
Hauptverfasser: Bijlsma, Pieter B., Peeters, Roger A., Groot, Jack A., Dekker, Pieter R., Taminiau, Jan A.J.M., Van Der Meer, Roelof
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container_issue 3
container_start_page 687
container_title Gastroenterology (New York, N.Y. 1943)
container_volume 108
creator Bijlsma, Pieter B.
Peeters, Roger A.
Groot, Jack A.
Dekker, Pieter R.
Taminiau, Jan A.J.M.
Van Der Meer, Roelof
description Background/Aims : 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.
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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.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1016/0016-5085(95)90440-9</identifier><identifier>PMID: 7875471</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Edetic Acid - pharmacokinetics ; Electrophysiology ; Female ; Gastroenterology. Liver. Pancreas. 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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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Edetic Acid - pharmacokinetics</subject><subject>Electrophysiology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Guinea Pigs</subject><subject>Horseradish Peroxidase - pharmacokinetics</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - physiology</subject><subject>Lactulose - pharmacokinetics</subject><subject>Lactulose - urine</subject><subject>Malformations</subject><subject>Mannitol - pharmacokinetics</subject><subject>Mannitol - urine</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Osmotic Pressure</subject><subject>Permeability</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Solutions - pharmacology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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identifier ISSN: 0016-5085
ispartof Gastroenterology (New York, N.Y. 1943), 1995-03, Vol.108 (3), p.687-696
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subjects Animals
Biological and medical sciences
Edetic Acid - pharmacokinetics
Electrophysiology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Guinea Pigs
Horseradish Peroxidase - pharmacokinetics
Intestinal Mucosa - metabolism
Intestinal Mucosa - physiology
Lactulose - pharmacokinetics
Lactulose - urine
Malformations
Mannitol - pharmacokinetics
Mannitol - urine
Medical sciences
Models, Biological
Osmotic Pressure
Permeability
Rabbits
Rats
Solutions - pharmacology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
title Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: A hypothesis
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