Linked Life Data

1970766

Source:http://linkedlifedata.com/resource/pubmed/id/1970766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-6-14
pubmed:abstractText
The disposition of 4'-hydroxypropranolol (HOP) was determined after iv administration to dogs (2 mg/kg; N = 5) and the pharmacokinetic parameters were calculated from plasma measurements. The clearance of HOP, 66 +/- 6 ml/min/kg (mean +/- SE), was considerably higher than that of propranolol previously determined, suggesting extrahepatic as well as hepatic clearance of HOP. The plasma half-life of HOP, 77 +/- 6 min, was shorter than that of propranolol. Although HOP is considerably less lipophilic than propranolol, its volume of distribution, 6.4 +/- 0.8 liter/kg, surprisingly, was larger. Like propranolol, HOP appeared to be cleared entirely by metabolism. Whereas propranolol is metabolized mainly by oxidation, HOP was metabolized to sulfate (HOPS) and glucuronic acid (HOPG) conjugates. The plasma half-lives of these conjugates were 2 to 3 times longer than for HOP, reflecting a slow, continuous formation from HOP. This was established for HOPS by iv administration of synthetic HOPS. Morover, after HOP administration both formation and renal clearance of HOPS were stereoselective in favor of the R-enantiomer. In summary, the main conclusion of this study is that the large volume of distribution as well as high clearance through sulfation and glucuronidation may explain the low plasma HOP levels observed during propranolol therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-4
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Pharmacokinetics and metabolism of the pharmacologically active 4'-hydroxylated metabolite of propranolol in the dog.
pubmed:affiliation
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.