Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
|
pubmed:dateCreated |
1997-3-18
|
pubmed:abstractText |
Extrahepatic drug metabolism was studied in an anhepatic rabbit model. Plasma concentrations of 4-methylumbelliferone (4-MU) and its major metabolites, 4-methylumbelliferyl-O-glucuronide and 4-methyumbelliferyl sulfate, along with lidocaine and its major metabolites, monoethylglycinexylidide and 3-hydroxylidocaine, were measured in sham rabbits (n = 4) and anhepatic rabbits (n = 4) following bolus intravenous administration of each drug. Along with concentration profiles of the drugs and metabolites, pharmacokinetic analyses of 4-MU metabolism and lidocaine metabolism were used to assess the extrahepatic metabolism of these classical substrates. Total body clearance of 4-MU in the anhepatic rabbits was about 50% that of the sham animals. Extensive extrahepatic glucuronidation of 4-MU was revealed by comparing the AUC ratios of 4-methylumbelliferyl-O-glucuronide and 4-MU in anhepatic and sham rabbit groups. Sulfation of 4-MU was reduced significantly in the anhepatic group, although some extrahepatic sulfation was observed. Total body clearance of lidocaine was reduced 3-fold in anhepatic animals. 3-Hydroxylidocaine was only detected in plasma samples from sham animals. These results emphasize the importance of extrahepatic sites in drug metabolism, especially glucuronidation of phenolic compounds such as 4-MU.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anesthetics, Local,
http://linkedlifedata.com/resource/pubmed/chemical/Hymecromone,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Lidocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Umbelliferones
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0090-9556
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
24
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
643-8
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:8781779-Anesthetics, Local,
pubmed-meshheading:8781779-Animals,
pubmed-meshheading:8781779-Disease Models, Animal,
pubmed-meshheading:8781779-Hepatectomy,
pubmed-meshheading:8781779-Hymecromone,
pubmed-meshheading:8781779-Indicators and Reagents,
pubmed-meshheading:8781779-Lidocaine,
pubmed-meshheading:8781779-Rabbits,
pubmed-meshheading:8781779-Umbelliferones
|
pubmed:year |
1996
|
pubmed:articleTitle |
Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit.
|
pubmed:affiliation |
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|