Effect of pretreatment with spironolactone, phenobarbital or β-diethylaminoethyl diphenylpropyl-acetate (SKF 525-A) on tritium levels in blood, heart and liver of rats at various times after administration of [ 3H]digitoxin

Abstract

The influence of spironolactone, phenobarbital and β-diethylaminoethyl diphenylpropylacetate (SKF 525-A) pretreatment on the tritium levels in blood, liver and heart of rats given [ 3H]digitoxin was investigated at various time periods. Blood tritium levels of spironolactone-pretreated rats were significantly lower than control animals 1 hr (38 per cent of control), 2 hr (26 per cent of control), 4 hr (38 per cent of control) and 8 hr (6 per cent of control) after i.p. injection of [ 3H]digitoxin. Tritium levels in the blood of phenobarbital-pretreated animals were not different from control animals at any of the time periods. SKF 525-A-pretreated animals had blood levels of tritium less than control animals at 1 hr (64 per cent of control) and greater than control animals at 8 hr (174 per cent of control), but were not different from control animals at either 2 or 4 hr. Radioactivity in the heart of spironolactone-pretreated animals was less than that in control animals at all but the 1-hr time interval, while radioactivity in phenobarbital-pretreated animals was not different from that of control animals at any time period and in SKF 525-A-pretreated animals was different only at the 8-hr period (172 per cent of control). Tritium levels in the liver of rats pretreated with spironolactone were greater than control animals at 1 hr (140 per cent of control) and less at 4 hr (66 per cent of control), but were not different at 2 or 8 hr. Phenobarbital pretreatment altered liver levels of tritium only at 1 hr (141 per cent of control), while SKF 525-A did not affect liver levels of radioactivity at any time period. These results indicate that spironolactone pretreatment markedly increases the metabolism and/or excretion of digitoxin, while phenobarbital pretreatment apparently does not affect these processes. The apparent inhibitory effects of SKF 525-A on digitoxin metabolism are seen only at 8 hr after the administration of digitoxin.