Document Detail


Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility.
MedLine Citation:
PMID:  7971714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The absorption of the polar drug phenol red was assessed in a rat intestinal perfusion model, in the presence of a variety of potential intestinal permeability enhancers. Both the absorption rate constant KA and the plasma phenol red concentration were measured. Perfusates were also assayed for the presence of lactate dehydrogenase (LDH) and lipid phosphate, as biochemical markers of intestinal wall damage. Histological evaluation of surfactant-perfused intestines was also carried out. The potential permeability enhancers studied were the surfactants sodium dodecyl sulfate (SDS), sodium taurocholate (TC), sodium taurodeoxycholate (TDC), polysorbate-80 (PS-80), and nonylphenoxypolyoxyethylene (NP-POE) with an average polar group size of 10.5 POE units. Among these, SDS and NP-POE-10.5 were the most potent permeability enhancers. The bile salt TDC was a more effective enhancer than the more polar TC. The polar non-ionic surfactant PS-80 was an ineffective enhancer. Phenol red KA and plasma level were generally correlated with biochemical and histological measures of intestinal damage. These observations indicate that permeability enhancement and local damage are closely related sequelae of the interaction of surfactants with the intestinal wall, and suggest that local wall damage may be involved in the mechanism of permeability enhancement. The reversibility of permeability enhancement and acute local damage was assessed for the surfactants TDC and NP-POE-10.5. Enhancement of phenol red permeability was reversed within 1-2 hr of the cessation of enhancer treatment. Biochemical markers of local damage also fell to control values within 1-2 hr of removal of enhancer from the perfusate. Histological evaluation of perfused intestines revealed that morphological damage was reversed within 3 hr. These results demonstrate that surfactant-induced acute intestinal wall damage is rapidly repaired.
Authors:
E S Swenson; W B Milisen; W Curatolo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmaceutical research     Volume:  11     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-12-23     Completed Date:  1994-12-23     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1132-42     Citation Subset:  IM    
Affiliation:
Pharmaceutical R&D Department, Central Research Division, Pfizer, INC 06340.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers
Chromatography, Thin Layer
Intestinal Absorption / drug effects*
Intestinal Mucosa / cytology,  drug effects,  enzymology
L-Lactate Dehydrogenase / metabolism
Male
Perfusion
Phenolsulfonphthalein
Phospholipids / metabolism
Rats
Rats, Inbred Strains
Stimulation, Chemical
Surface-Active Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Phospholipids; 0/Surface-Active Agents; 143-74-8/Phenolsulfonphthalein; EC 1.1.1.27/L-Lactate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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