NEUROTOXICITY OF DIGITOXIN IN ADULT AND NEWBORN RATS - DRUG DISTRIBUTION

  • 1 January 1976
    • journal article
    • research article
    • Vol. 224  (1) , 4-12
Abstract
ECG monitoring of adult and 1 wk 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 was 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 wk old (weanling) rats at 2, 12 and 24 h. 3H-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 h), 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 h) suggesting that digitoxin metabolites may be potent cerebrotoxins. Extremely high adrenal concentrations were noted in all animals.