Linked Life Data

1871038

Source:http://linkedlifedata.com/resource/pubmed/id/1871038

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1991-9-17
pubmed:abstractText
Dexamethasone-beta-D-glucoside is a potential prodrug for colonic delivery of the antiinflammatory agent, dexamethasone. The ability of this prodrug to deliver dexamethasone selectively to the colon depends not only on its being slowly absorbed from the alimentary canal, but also on its having chemical and enzymatic stability in the stomach and small intestine. Once reaching the large bowel, it should be quantitatively hydrolyzed to release the active agent. The potential of dexamethasone-beta-D-glucoside for colon-specific delivery of dexamethasone is assessed by determining the rates of its hydrolysis down the alimentary canal of the guinea pig, an animal in which an inflammatory bowel disease model has been developed. The hydrolytic activity is examined in tissues and luminal contents of the stomach, proximal and distal segments of the small intestine, cecum, and colon. For the tissues, the greatest hydrolytic activity is in the proximal small intestine, while the stomach, cecum, and colon have only moderate activity. In contrast, the contents of the cecum and colon show greater activity than the contents of the small intestine and stomach. The luminal contents retained beta-glucosidase activity even after repeated centrifugation and resuspension in a buffer. The activity was unaffected by homogenization. These observations suggest that hydrolytic activity is associated with enzymes located on the surface of luminal cells. The movement and hydrolysis of dexamethasone-beta-D-glucoside down the gastrointestinal tract of the guinea pig are also examined. About 20 to 30% of an oral dose appears to reach the cecum. Here the prodrug is rapidly hydrolyzed to the active drug. From intravenous administration of the prodrug and drug, it is apparent that dexamethasone-beta-D-glucoside is poorly absorbed in the gastrointestinal tract (bioavailability, less than 1%). There is a ninefold selective advantage for delivery of dexamethasone in cecal tissues in the guinea pig under the conditions of this experiment. Thus, there is a potential for a decrease in the usual dose and a concomitant reduction in the systemic exposure to dexamethasone. Because humans have much less glucosidase activity in the small intestine, even greater site-selective delivery to the cecum and colon is expected.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0724-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Colon-specific delivery of dexamethasone from a glucoside prodrug in the guinea pig.
pubmed:affiliation
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't