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

Digoxin serum concentrations were measured by a routine radioimmunoassay in 30 neonates not receiving digoxin; nonetheless, digoxin levels were between 0.17nM and 1.64nM (X = 0.64nM ± 0.27nM). There was a negative correlation between gestational age and concentration of an endogenous digoxin-like substance (EDLS). Neonates ≤32 wk gestational age had higher levels of EDLS than neonates >32 wk old. EDLS concentrations were compared in 22 mothers and their 24 offspring and were higher in all newborn infants (0.34nM ± 0.09nM and 0.15nM ± 0.08nM). EDLS was shown to inhibit Na⁺-K⁺-adenosinetriphosphatase 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 0.6nM EDLS would lengthen the digoxin t 1 2 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 nglml would increase the t 1 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.