Linked Life Data

14534358

Source:http://linkedlifedata.com/resource/pubmed/id/14534358

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-12-3
pubmed:abstractText
The disposition kinetics of O-butyryl propranolol (butyryl-PL), a model compound containing an ester moiety, after intravenous administration was compared with that of PL in rats and beagle dogs. Rats showed only 30% conversion of butyryl-PL to PL up to 2 h after dosing, whereas dogs showed nearly complete conversion within 10 min after administration. The CL(total) of butyryl-PL in rats was 5.8 l/h/kg and that in dogs was 65.6 +/- 18.6 l/h/kg, both of which were greater than hepatic blood flow. The in vivo conversion from butyryl-PL to PL in the rat could be explained on the basis of the hydrolysis characteristics in the liver and blood. The in vitro hydrolysis data and the in vivo data after intra-arterial administration clearly demonstrated that the extremely high CL(total) of butyryl-PL in dogs was dependent on first-pass hydrolysis in the lung in addition to hydrolysis at a blood flow-limited rate in the liver and kidney. The availability of butyryl-PL after passage through the lung was 50%. Furthermore, the isoform of carboxylesterase involved in the pulmonary hydrolysis of butyryl-PL in the dog was identified as D1, a CES-1 group enzyme. However, butyryl-PL was not recognized as a substrate by CES-1 family carboxylesterases, which are present at high levels in the rat lung (RH-1) and kidney (RL-1). These findings indicate that extrahepatic metabolism, especially in the lung, is important in the disposition of drugs containing an ester moiety after intravenous administration and that the substrate specificity of carboxylesterase isozyme distinguishes from others.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
307
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1234-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14534358-Adrenergic beta-Antagonists, pubmed-meshheading:14534358-Algorithms, pubmed-meshheading:14534358-Animals, pubmed-meshheading:14534358-Antibodies, Blocking, pubmed-meshheading:14534358-Area Under Curve, pubmed-meshheading:14534358-Carboxylic Ester Hydrolases, pubmed-meshheading:14534358-Chromatography, High Pressure Liquid, pubmed-meshheading:14534358-Cytosol, pubmed-meshheading:14534358-Dogs, pubmed-meshheading:14534358-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:14534358-Enzyme Inhibitors, pubmed-meshheading:14534358-Hydrolysis, pubmed-meshheading:14534358-Injections, Intra-Arterial, pubmed-meshheading:14534358-Injections, Intravenous, pubmed-meshheading:14534358-Isoenzymes, pubmed-meshheading:14534358-Lung, pubmed-meshheading:14534358-Male, pubmed-meshheading:14534358-Microsomes, pubmed-meshheading:14534358-Nitrophenols, pubmed-meshheading:14534358-Propranolol, pubmed-meshheading:14534358-Rats, pubmed-meshheading:14534358-Rats, Wistar, pubmed-meshheading:14534358-Species Specificity, pubmed-meshheading:14534358-Stereoisomerism
pubmed:year
2003
pubmed:articleTitle
Evidence for the involvement of a pulmonary first-pass effect via carboxylesterase in the disposition of a propranolol ester derivative after intravenous administration.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan. iteruko@gpo.kumamoto-u.ac.jp
pubmed:publicationType
Journal Article