Neurotoxicity of digitoxin in adult and newborn rats: drug distribution.
Electrocardiographic monitoring of adult and 1 week old (newborn) rats during severe acute digitoxin toxicity demonstrated a lack of acrdiotoxicity 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 (greater than 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.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D004074:Digitoxin / Q000378:metabolism / Q000633:toxicity*; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013997:Time Factors
D004074:Digitoxin