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Maturation and renal digoxin clearance
Insights
Digoxin clearance relative to creatinine clearance is higher in children than adults, indicating reduced renal tubular secretion at puberty. This impacts pediatric digoxin dosing and renal physiology.
Area of Science:
- Pharmacology
- Nephrology
- Pediatrics
Background:
- Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
- Renal excretion is the primary route of digoxin elimination.
- Maturation-related changes in renal function may affect digoxin disposition.
Purpose of the Study:
- To investigate the impact of maturation on the renal disposition of digoxin.
- To determine how the ratio of digoxin clearance to creatinine clearance changes with age.
Main Methods:
- Studied 35 patients aged 3 days to 79 years at steady-state digoxin levels.
- Measured digoxin clearance and creatinine clearance.
- Calculated the ratio of digoxin clearance to creatinine clearance.
Main Results:
- The mean digoxin clearance/creatinine clearance ratio was 1.49 in prepubertal children and infants (≥2 months).
- The mean ratio decreased significantly to 0.82 in sexually mature adults (P < 0.005).
- A decrease in net renal tubular secretion of digoxin was observed around puberty.
Conclusions:
- Renal tubular secretion of digoxin decreases at puberty.
- This developmental change in renal tubular physiology may explain higher digoxin doses needed in children.
- Findings suggest broader implications for understanding pediatric renal tubular function.
Abstract:
To evaluate the effect of maturation on the renal disposition of digoxin, the ratio of digoxin clearance to creatinine clearance was determined in 35 patients who were 3 days to 79 yr old. All were at steady-state levels for digoxin treatment. A mean ratio of 1.49 +/- 0.67 (SD) was obtained in the group of prepubertal children and infants greater than or equal to 2 mo of age. The mean ratio decreased to 0.82 +/- 0.25 (SD) in the adult group; adults were defined as sexually mature adolescents or older (P less than 0.005). The decrease in net renal tubular secretion of digoxin appears to occur at puberty. This observation can provide one explanation for the apparently larger doses of digoxin required by infants and children than by adults. It may also represent a developmental change in renal tubular physiology with broader significance than for digoxin disposition alone.