Linked Life Data

2123007

Source:http://linkedlifedata.com/resource/pubmed/id/2123007

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1990-12-31
pubmed:abstractText
A genetically determined pharmacokinetic and pharmacodynamic interaction between quinidine and single doses of encainide in healthy volunteers has previously been described. In subjects with the extensive metabolizer phenotype, quinidine blunted encainide-induced QRS prolongation (a marker of sodium channel block) because it impaired encainide biotransformation to the potent active metabolites O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide. Therefore, the purpose of this study was to test the hypothesis that quinidine would inhibit sodium channel block (and by inference arrhythmia suppression) during encainide therapy in patients with the extensive metabolizer phenotype. Surprisingly, however, in eight extensive metabolizer patients, the extent of QRS prolongation during chronic encainide therapy was unaltered by quinidine (139 +/- 21 vs. 139 +/- 22 msec) whereas arrhythmia suppression was enhanced (64 +/- 22 to 77 +/- 19%; P = .05). Plasma concentration data demonstrated that although encainide metabolism to ODE was partially impaired by quinidine, subsequent 3-methoxy-O-desmethyl encainide formation from ODE was virtually completely inhibited; thus steady-state plasma ODE remained unchanged whereas plasma encainide increased 10-fold (21 +/- 30 to 240 +/- 118 ng/ml; P less than .05). In contrast, no changes in disposition or in pharmacodynamics were observed in two poor metabolizers. It is concluded that the effect of this drug interaction in patients is determined by differential sensitivities to inhibition by quinidine of encainide O-demethylation and subsequent ODE 3-methoxylation. Evaluation of potential drug interactions should include assessment of possible genetic factors as well as of steady-state effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
255
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
642-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Genetically determined steady-state interaction between encainide and quinidine in patients with arrhythmias.
pubmed:affiliation
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't