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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-6-16
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pubmed:abstractText |
The use of class I antiarrhythmic drugs may be complicated by the presence of active metabolites. A simple technique to predict the clinical activity of these metabolites might help with the clinical use of these drugs. We tested the hypothesis that drug metabolites bind to the class I drug receptor, but that only clinically active metabolites bind appreciably at clinically observed concentrations. Using a radioligand assay, we determined whether 13 class I drug metabolites interacted with a receptor for class I drugs associated with the cardiac sodium channel. The radioligand was [3H]batrachotoxinin A20 benzoate. All 13 metabolites bound to the drug receptor with IC50 values of 2.7 to 375 microns, and a mean Hill number of 1.0 +/- 0.3. All of the seven active metabolites (N-acetylprocainamide, mono-N-dealkyldisopyramide, 5-hydroxypropafenone, N-desisopropylpropafenone, 0-demethylencainide, 3-methoxy-0-demethylencainide and desethylamiodarone) each bound to the receptor at concentrations approaching their clinical concentrations, whereas none of the six inactive metabolites (quinidine-N-oxide, 3-hydroxyquinidine, glycinexylidide, monoethylglycinexylidide, N-demethylencainide and N,0-demethylencainide) did. Using a relationship which correlates drug IC50 values and clinically observed drug concentrations we calculated predicted clinical concentrations if the metabolites were clinically active. A predicted/observed ratio < or = 10 correlates with 100% positive and negative accuracies whether a drug metabolite has clinical activity. Thus a simple radioligand assay predicts whether class I drugs have clinical activity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
477-81
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading | |
pubmed:year |
1994
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pubmed:articleTitle |
Interaction of drug metabolites with the class I antiarrhythmic drug receptor on rat cardiac myocytes.
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pubmed:affiliation |
Cardiovascular Research Group, University of Calgary, Alberta, Canada.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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