Linked Life Data

9058530

Source:http://linkedlifedata.com/resource/pubmed/id/9058530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-7-8
pubmed:abstractText
1. Fluparoxan is an alpha 2-adrenoceptor antagonist that has a relatively planar, tricyclic structure and was considered a potential substrate and inducer of cytochrome P4501A (CYP1A) enzymes. 2. Structure-activity analysis indicated some potential for CYP1A interaction, although its greater log P and molecular depth, compared with many CYP1A inducers, suggested fluparoxan would be a weak ligand for the aryl hydrocarbon (Ah) receptor and only a weak inducer. 3. In vitro, fluparoxan showed little affinity for the CYP1A enzymes. The compound was not metabolized by human CYP1A1 or 1A2 heterologously expressed in yeast and its rate of metabolism in rat and human microsomes was unaffected by the addition of the 1A inhibitor alpha-naphthoflavone. Furthermore, Ki's for fluparoxan against EROD activity were > 4000-fold higher than those of alpha-naphthoflavone. 4. In vivo, however, fluparoxan did show some capacity for CYP1A induction. In rat, hepatic EROD activity increased approximately 40-fold with seven once-daily oral doses of fluparoxan (50 mg/kg, solution), and immunoblotting studies confirmed induction of CYP1A2, though not of 1A1. In man, administration of 11 twice-daily oral doses of fluparoxan (8 mg tablet) produced some reduction in plasma levels of orally administered phenacetin and in the ratio of phenacetin AUC/urinary paracetamol, consistent with increased O-deethylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-73
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Cytochrome P4501A (CYP1A) induction in rat and man by the benzodioxino derivative, fluparoxan.
pubmed:affiliation
Bioanalysis and Metabolism Division, Glaxo Wellcome Research and Development, Ware, UK.
pubmed:publicationType
Journal Article