Linked Life Data

6267246

Source:http://linkedlifedata.com/resource/pubmed/id/6267246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1981-10-25
pubmed:abstractText
Repetitive oral administration of propranolol to rats (100 mg/kg/day for 5 days) resulted in a marked inhibition of hepatic microsomal metabolism of propranolol when incubated at low initial substrate concentrations (less than 2 microM). Associated with the inhibition of propranolol metabolism was a significant reduction in metabolites derived from naphthalene ring oxidation and an increased formation of N-desisopropylpropranolol. In vivo studies after propranolol pretreatment resulted in: an increased hepatic concentration and an increased systemic availability of propranolol; a decreased hepatic and plasma concentration of polar metabolites; and an increased plasma concentration of metabolites derived from propranolol N-dealkylation. Propranolol was converted both in vitro and in vivo by a hepatic microsomal mixed-function oxidase to a reactive metabolite capable of covalently binding with microsomal macromolecules. We propose that selective covalent binding of the reactive intermediate to the molecular form of cytochrome P-450 that ring hydroxylates propranolol would account for the marked inhibition of propranolol metabolism in vitro and for the increased systemic availability of propranolol in vivo after pretreatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
218
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
The inhibitory effect of propranolol pretreatment on its own metabolism in the rat.
pubmed:publicationType
Journal Article, In Vitro