Maturation of renal tubular transport of digoxin

Previous data have suggested an age-related increase in renal tubular secretion of digoxin in infants and children receiving longterm digoxin therapy. This phenomenon could be the result of a maturational process or secondary to chronic substrate stimulation. To investigate this question, two groups of 2-week-old paired littermate rats received intraperitoneal injections of either digoxin or an equal volume of normal saline (control) on alternate days until sacrificed at 4, 6, and 8 wk of age. An additional group of 12- wk-old rats were studied as controls.¹²⁵I-labeled digoxin uptake was measured in renal cortical slices as the cPM/mg wet tissue slice/medium ratio (S/M). Both digoxin-treated and control rats demonstrated significant age-related increments in digoxin uptake. S/M ratios at 4, 6, 8, and 12 wk in the control group were 1.34 ± 0.06, 1.39 ± 0.14, 1.62 ± 0.18 and 1.93 ± 0.23, respectively (mean ± S.D.) (r = 0.81; P < 0.001). S/M ratios in the digoxin- treated animals at 4, 6, and 8 wk were 1.28 ± 0.16, 1.33 ± 0.09, and 1.52 ± 0.23, respectively (r = 0.50; P < 0.025), but did not differ significantly at each age from those in the control group.¹²⁵I uptake was significantly reduced by both dinitrophenol and sodium azide, as well as by a 100% nitrogen atmosphere. These results indicate that renal tubular transport of digoxin is an age-related energy dependent process which probably is not subject to substrate stimulation. Speculation An age-dependent increase in renal digoxin excretion exists in treated infants and children. This augmentation is due to nonspecific renal maturational phenomena and not to specific substrate induced tubular transport.