Serum levels of digoxin in infants and children

Krasula, Richard W.; Pellegrino, P A; Hastreiter, Alois R.; Soyka, Lester F.

doi:10.1016/s0022-3476(72)80193-8

Cited by 32 publications

(9 citation statements)

References 8 publications

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“…Infants and children of various ages achieve the same 'mean plateau' serum concentration of digoxin (measured 5 to 7 hours after an oral dose) despite a weight·adjusted dosage which decreases 9 with age according to Krasula et al (1972) in table V. P ossible explanations for this include lower absorption in the younger age groups, or decreasing metabolic o r renal clearance with age. However, the same authors also measured the post·absorptive serum concentrations which in all groups were proportional to the given dose.…”

Section: Digoxinmentioning

confidence: 99%

Clinical Pharmacokinetics in Infants and Children

Rane

Wilson

1976

Clinical Pharmacokinetics

127

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Wide variations in drug dose recommendations for children of the same or different ages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics in children. Selected aspects of available literature on pharmacokinetics of drugs used in older infants and children has been reviewed with special attention to calculation of an age-appropriate dose. During the neonatal period and early infancy the elimination of many drugs that are excreted in the urine in unchanged form is restricted by the immaturity of glomerular filtration and renal tubular secretion. On the other hand, in late infancy and/or in childhood, a similar or greater rate of elimination from plasma than in adults has been observed for many drugs, notably digoxin, phenobarbitone, phenytoin, carbamazepine, ethosuximide, diazoxide, clindamycin and propoxyphene. Consistent with this, it has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult. This is true for phenobarbitone, phenytoin and ethosuximide. Some age groups of children remain uninvestigated with regard to pharmacokinetics, even for the drugs reviewed. Therefore, pediatric therapy remains empirically based for many drugs.

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Section: Digoxinmentioning

confidence: 99%

Clinical Pharmacokinetics in Infants and Children

Rane

Wilson

1976

Clinical Pharmacokinetics

127

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“…This implies that the renal excretion of digoxin during this period increases with age. As a possible reason for the requirement of larger doses of digoxin in infants, it has been suggested that they have a more rapid renal excretion of the glycoside than children and adults (Krasula et al, 1972). Another possibility is that there is a metabolic degradation in infants greater than currently believed ( Morselli et al, 1975).…”

Section: 3 Eliminationmentioning

confidence: 99%

“…If the daily amount of digoxin is given in 2 equal doses with an interval of 12 hours (Cree et al, 1973), the samples should preferably be taken immediately before administration of the next dose (or from 6 to 8 to I 2 hours after the previous oral intake). Krasula et al (1972) 6 mths -2 yrs 9 ··0.020…”

Section: Serum Digoxin Concentrations During Maintenance Therapymentioning

confidence: 99%

Clinical Pharmacokinetics of Digoxin in Infants

Wettrell

Andersson

1977

Clinical Pharmacokinetics

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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. 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.

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“…These differences may be compensated to a certain extent by higher serum concentrations of the drug as seen in clinical practice (14,18) or by improved uptake of digitalis glycosides by the newborn myocardium (1, 11) resulting in an increased sensitivity of infant myocardium to digitalis. It is not known whether higher serum concentrations of digoxin frequently seen in infants in clinical settings have further inotropic advantages over the lower serum concentrations commonly observed in the adult.…”

Section: Discussionmentioning

confidence: 99%

Ouabain-Induced Inotropism of Isolated Newborn and Adult Rabbit Myocardium

Park¹

1981

Dev Pharmacol Ther

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Relative sensitivities to ouabain of atrial and ventricular muscles from 1-week and 4-month rabbits were compared in vitro. Ventricular muscles were also studied with prior treatment that minimized unphysiological, stimulation-induced release of norepinephrine (propanolol and/or reserpinization). Atrial and pretreated ventricular muscles from the newborn showed (a) higher sensitivity to ouabain and (b) the same ‘relative’ positive inotropic effect (RPIE) when compared to those of the adult (RPIE is ouabain-induced inotropism relative to the maximal calcium-induced inotropism and represents ouabainspecific inotropism). With no prior treatment, ventricular muscles from the newborn showed a nonsignificant tendency toward a lower sensitivity to ouabain and a significantly lower RPIE than those of the adult. These results suggest that under normal physiological conditions, the newborn myocardium may be more sensitive to ouabain than that of the adult.

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Serum levels of digoxin in infants and children

Cited by 32 publications

References 8 publications

Clinical Pharmacokinetics in Infants and Children

Clinical Pharmacokinetics in Infants and Children

Clinical Pharmacokinetics of Digoxin in Infants

Ouabain-Induced Inotropism of Isolated Newborn and Adult Rabbit Myocardium

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