Source:http://linkedlifedata.com/resource/pubmed/id/11318520
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2001-4-24
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0163-2116
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
489-94
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11318520-Animals,
pubmed-meshheading:11318520-Biological Availability,
pubmed-meshheading:11318520-Female,
pubmed-meshheading:11318520-Portacaval Shunt, Surgical,
pubmed-meshheading:11318520-Sorbitol,
pubmed-meshheading:11318520-Splanchnic Circulation,
pubmed-meshheading:11318520-Swine
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pubmed:year |
2001
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pubmed:articleTitle |
Time-dependent modifications of splanchnic circulation in female pigs submitted to end-to-side portacaval anastomosis.
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pubmed:affiliation |
Divisione di Medicina Generale A, A.O. San Giovanni Battista, Turin, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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