Significance of the endogenous digoxin-like substance in infants and mothers

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Abstract
Digoxin serum concentrations were measured by a routine radioimmunoassay in 30 neonates not receiving digoxin: nonetheless, digoxin levels were between 0.17 nM and 1.64 nM (.hivin.X [mean] = 0.64 nM .+-. 0.27 nM). There was a negative correlation between gestational age and concentration of an endogenous digoxin-like substance (EDLS). Neonates .ltoreq. 32 wk gestational age had higher levels of EDLS than neonates > 32 wk old. EDLS concentrations were compared in 2 mothers and their 24 offspring and were higher in all newborn infants (0.34 nM .+-. 0.09 nM and 0.15 nM .+-. 0.08 nM). EDLS was shown to inhibit Na+-K+-ATPase activity by measurement of 86Rb uptake in erythrocytes exposed to sera samples from 30 infants in the study. EDLS levels > 0.6 ng/ml were associated with lesser 86Rb uptake. Simulation kinetics suggest that the presence of 0.6 nM EDLS would lengthen the digoxin t1/2 [half-life] by 64%, reduce the volume of distribution by 23%, and lower clearance by 53% if the peak "true" digoxin level were 2 ng/ml. EDLS concentrations of 1.5 ng/ml would increase the t1/2 by 207% while reducing the volume of distribution by 43% and clearance by 81%. These considerations cast serious doubts on the validity of currently accepted digoxin kinetics and dosing in preterm infants.

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