CORRELATION BETWEEN THE DISPOSITION OF [C-14]LABELED CLOFILIUM AND ITS CARDIAC ELECTRO-PHYSIOLOGICAL EFFECT

  • 1 January 1982
    • journal article
    • research article
    • Vol. 221  (3) , 584-589
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 h, 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 h. Plasma levels of radioactivity rapidly decline in rats and dogs administered 5 mg/kg of [14C]clofilium characterized by a plasma radioactivity half-life [t1/2] for the elimination phase of 2.5-3 h. Tissue levels of radioactivity were persistent; the t1/2 of radioactivity in the rat heart was 5 days and 14 days in the dog heart. At 24 h 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 t1/2 of the effect of clofilium on action potential duration was 10 days which is in agreement with the persistence of radioactivity in tissues. Evidently, [14C]clofilium and/or metabolites concentrate in the heart and plasma levels of radioactivity may not be an accurate index cardiac levels or biological response.