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 long-term 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 he 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 less than 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 less than 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.