Electrocardiographic monitoring of adult and 1 week old (newborn) rats during severe acute digitoxin toxicity demonstrated a lack of cardiotoxicity despite marked neurotoxicity in both age groups. To examine the possibility that drug disposition is a factor in the unusual digitoxin sensitivity of newborn rats, 3H digitoxin distribution in liver, heart, brain, kidney, adrenal, blood and fat was compared in 1 and 3 week old (weanling) rats at 2, 12 and 24 hr. H3 label was rapidly sequestered by the liver in weanlings but not in newborn rats. Newborns had significantly higher concentrations of 3H substance in all other organs, particularly in brain (>25% of the administered dose at 24 hr), indicating a cerebrotoxic basis for the newborn's sensitivity to digitoxin. Only trace amounts of 3H substance were recovered from adult rat brain during severe neurotoxicity (72 hr) suggesting that digitoxin metabolites may be potent cerebrotoxins. Extremely high adrenal concentrations were noted in all animals.
|Original language||English (US)|
|Number of pages||9|
|Journal||Archives Internationales de Pharmacodynamie et de Therapie|
|State||Published - Dec 1 1976|
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