Linked Life Data

3919554

Source:http://linkedlifedata.com/resource/pubmed/id/3919554

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1985-4-19
pubmed:abstractText
Flecainide acetate, an investigational class 1 antiarrhythmic agent, undergoes biotransformation in man with production of 2 major metabolites: meta-O-dealkylated flecainide (S-24623) and the meta-O-dealkylated lactam of flecainide (S-26191). This study compared the effects of flecainide, S-24623 and S-26191 on cardiac electrophysiologic characteristics in the anesthetized dog. Each dog received 2 dose levels of 1 of the 3 test compounds after control measurements. Flecainide (2 and 4 mg/kg in 8 dogs), S-24623 (4 and 8 mg/kg in 8 dogs) and S-26191 (4 and 10 mg/kg in 7 dogs) were administered intravenously in dilute solution. Of the 3 compounds, only flecainide significantly prolonged sinus cycle length (p less than 0.01). However, both flecainide and S-24623 significantly prolonged minimum atrial paced cycle length with 1:1 atrioventricular conduction, atrioventricular nodal effective and functional refractory periods, and right ventricular effective refractory period. Metabolite S-26191 exhibited qualitatively similar but much weaker electrophysiologic actions. The maximal electrophysiologic effects of flecainide and S-24623 were approximately equivalent, but the metabolite was about one-half as potent on a milligram-permilligram basis, and lacked marked effects on infranodal (HV interval) conduction. S-26191 was less than one-tenth as potent as flecainide. Therefore, since both flecainide metabolites occur primarily in the conjugated form in plasma (i.e., free metabolite concentrations are low), it is unlikely that these compounds either potentiate flecainide's antiarrhythmic action or increase susceptibility to drug toxicity in the clinical setting.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-9149
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
807-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Electrophysiologic effects of flecainide acetate and its major metabolites in the canine heart.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't