Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-4-24
pubmed:abstractText
Fractional systemic bioavailability of orally administered drugs was found to be unexpectedly low in liver cirrhosis, even after surgical portal-systemic shunting. Fecal loss or intestinal first-pass elimination were assumed to explain the finding. In this paper we evaluated alternative pathophysiological interpretations relating low bioavailability to adaptive circulatory modifications. D-Sorbitol was used because its hepatic extraction is very high and hepatic removal follows a flow-dependent clearance regimen. D-Sorbitol bioavailability was measured at steady state in pigs submitted to end-to-side portacaval anastomosis, immediately after surgery and four weeks later. Intestinal first-pass elimination dependent on fecal loss and intraluminal degradation was excluded by administering D-sorbitol into the superior mesenteric artery. Almost complete bioavailability was observed immediately after surgery (N = 6, 0.96+/-0.08); four weeks later the bioavailability dropped (-36.8+/-18.7%; P < 0.001) while hepatic clearance significantly increased (+83.6+/-47.9%; P < 0.01). Experimental data support the hypothesis that adaptive circulatory changes spontaneously occur after some time, leading to a lower than expected portal bioavailability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0163-2116
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Time-dependent modifications of splanchnic circulation in female pigs submitted to end-to-side portacaval anastomosis.
pubmed:affiliation
Divisione di Medicina Generale A, A.O. San Giovanni Battista, Turin, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't