Brain, myocardium and plasma concentrations and toxicity of digoxin in newborn and adult rats.

Abstract

Digoxin tissue concentrations and elimination kinetics were determined to explore possible explanations of the age-related changes in response to digoxin in the rat. Digoxin concentrations were measured in brain, myocardium, and plasma of newborn and adult rats at serial time intervals after nontoxic doses and at the time of death after toxiequivalent doses. After SC administration of a nonlethal dose of 500 micrograms/kg digoxin, brain, myocardium and plasma concentrations and areas under the curve of digoxin concentrations vs time were considerably greater (P less than 0.01) in the newborn than in the adult rats. Following toxiequivalent doses of digoxin (2.5X LD50), digoxin concentrations were several fold greater in the myocardium and plasma of adult rats than in newborn specimens; in contrast, despite the 30-fold smaller digoxin dose per kilogram body weight given to 1-day-old rats, mean digoxin concentration was 2.9 times greater in their brain than in adult brain. These findings suggest that changes in tissue distribution and in the disposition of digoxin play a role in the greater sensitivity of newborn rats to digitoxicity and in the distinct digitoxic arrhythmic effects observed in the newborn as compared to the adult rat.