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Abstract

Correlation between the disposition of [14C]clofilium and its cardiac electrophysiological effect.

T D Lindstrom, P J Murphy, J K Smallwood, S A Wiest and M I Steinberg
Journal of Pharmacology and Experimental Therapeutics June 1982, 221 (3) 584-589;
T D Lindstrom
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P J Murphy
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J K Smallwood
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S A Wiest
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M I Steinberg
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Abstract

The disposition of [14C]clofilium was studied in rats and dogs and related to the electrophysiological effects observed in isolated canine Purkinje fibers. Ten percent of the dose of [14C] clofilium administered to rats and dogs i.v. was excreted in the urine within 72 hr, whereas 55% was excreted in the feces during the same period in both species. In rats, biliary excretion accounted for 35% of the dose within 48 hr. Plasma levels of radioactivity rapidly decline in rats and dogs administered 5 mg/kg of [14C]clofilium characterized by a plasma radioactivity half-life for the elimination phase of 2.5 to 3 hr. In contrast, tissue levels of radioactivity were persistent; the half-life of radioactivity in the rat heart was 5 days and 14 days in the dog heart. Twenty-four hours after an i.v. dose of clofilium (0.044-1.3 mg/kg) to dogs, the action potential duration of isolated Purkinje fibers was prolonged in a dose-dependent manner. The half-life of the effect of clofilium on action potential duration as 10 days which is in agreement with the persistence of radioactivity in tissues. The data suggest that [14C]clofilium and/or metabolites concentrate in the heart and that plasma levels of radioactivity may not be an accurate index of cardiac levels or biological response.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 221, Issue 3
1 Jun 1982
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Abstract

Correlation between the disposition of [14C]clofilium and its cardiac electrophysiological effect.

T D Lindstrom, P J Murphy, J K Smallwood, S A Wiest and M I Steinberg
Journal of Pharmacology and Experimental Therapeutics June 1, 1982, 221 (3) 584-589;

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Abstract

Correlation between the disposition of [14C]clofilium and its cardiac electrophysiological effect.

T D Lindstrom, P J Murphy, J K Smallwood, S A Wiest and M I Steinberg
Journal of Pharmacology and Experimental Therapeutics June 1, 1982, 221 (3) 584-589;
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