Clinical Pharmacokinetics of Digoxin in Infants

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Abstract
Based on clinical experience, infants with congestive heart failure are given larger doses of digoxin than adults, whether calculated on the basis of body weight or surface area. The reasons for this difference in dosage are not clear. The myocardium of the infants might be more resistant to the effects of digoxin than that of adults, and/or differences might exist between infants and adults concerning the absorption, distribution and elimination of the glycoside. Infants have been found to absorb digoxin in solution at the same rate and to the same extent as adults. The relative distribution of the glycoside to different tissues is also similar in the two age-groups. However, the binding of digoxin to several tissues seems to be more extensive in infants than in adults. In agreement with this, the apparent volume of distribution of the glycoside is larger in infants than in adults. In infants (except neonates), the elimination half-life of digoxin is shorter than in adults. As no enhanced urinary excretion has been found in infants there might be a non-renal elimination of the glycoside. With most prevailing dose schedules for digoxin, serum concentrations higher than those considered optimum for adults are often obtained in infants. It is known that infants tolerate higher serum digoxin concentrations than adults without developing signs of toxicity. However, it is not known whether such high concentrations are necessary for obtaining an adequate inotropic effect on the myocardium of the infants. If the relation between serum concentration and effect is the same in infants and adults, the loading (digitalising) dose generally given to infants is unnecessarily high.