Age dependant factors influencing digoxin pharmacokinetics in the postnatal puppy.

H3-digoxin pharmacokinetics following intravenous pulse injections was studied in dogs ranging in age from 0.5--2 days (n=2), 3--10 days (n=6), 11--30 days (n=5), 31--90 days (n=3) and adult dogs (n=5). All animals in each age group exhibited a biexponential elimination of H3-digoxin from the vascular compartment and data are analyzed by use of a two compartment pharmacokinetic model. Pharmacokinetic parameters showed significant age related differences. The mean T1/2(alpha) was greater in puppies aged 0.5--2 (8.92 +/- 2.61 min), 3--10 (11.8 +/- 1.99 min) and 11--30 days (10.32 +/- 1.89 min) when compared to adult dogs (5.36 +/- 0.91 min). The mean T1/2(beta) was four times longer in 3--10 day old dogs (1342.05 min) than in adult dogs (327.0 min) and decreased with increasing age of the puppies. The beta-phase rate constants were statistically different (p less than 0.05) between 3--10 day old and adult dogs. Elimination of H3-digoxin was slower in puppies than adult dogs (Kel in 3--10 day old puppies = 0.0046 min(-1); adult dogs = 0.0197 min(-1)) and was accompanied by a lower clearance of H3-digoxin in 3--10 day old puppies (2.05 ml/min/kg) than in adult dogs (7.41 ml/min/kg) [p less than 0.0001]. Functional immaturity of the canine kidney during early development probably constitutes the physiologic basis for the differences noted in H3-digoxin kinetics. While these distinctions in elimination kinetics are age related they do not clarify why younger organisms tolerate higher digoxin levels than adults with less apparent toxicity.