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Cumulative increase in serum furosemide concentration following repeated doses in the newborn
Insights
Repeat doses of furosemide (a diuretic) lead to higher drug levels in newborn plasma. This indicates potential accumulation, possibly due to reduced drug clearance in infants.
Area of Science:
- Neonatal pharmacology
- Clinical pharmacy
- Pediatric drug monitoring
Background:
- Furosemide is a common diuretic used in neonates.
- Understanding drug accumulation is crucial for safe and effective neonatal care.
Purpose of the Study:
- To investigate plasma accumulation of furosemide with repeated dosing in newborns.
- To assess the impact of repeated furosemide administration on drug concentrations.
Main Methods:
- Eight newborns received 1-mg/kg intravenous furosemide every 12 hours for four doses.
- Serum furosemide peak and trough concentrations were measured using High-Performance Liquid Chromatography (HPLC).
Main Results:
- Mean peak serum furosemide levels significantly increased with repeated doses (p < .05).
- Mean trough concentrations plateaued, suggesting a steady state was reached.
- Increased drug levels indicate potential plasma accumulation.
Conclusions:
- Repeat dosing of furosemide in newborns can lead to plasma accumulation.
- This accumulation is likely due to decreased plasma clearance or altered volume of distribution.
- Findings highlight the importance of monitoring furosemide levels in neonatal populations.
Abstract:
In order to test whether repeat doses of the diuretic furosemide result in plasma accumulation of this drug, eight newborns (mean birthweight, 1252 gm; mean gestational age, 27.5 weeks; mean postnatal age, 44.7 days; and normal renal function) were each given a 1-mg/kg iv bolus every 12 hr for four doses and maintained normally hydrated throughout the study period. Serum furosemide peak concentrations (1 hr after administration) were measured in eight newborns, and trough levels in four newborns, by HPLC. The mean 1-hr serum furosemide level increased with repeated doses of the drug, from 3.18 +/- 0.52 to 7.95 +/- 2.36 mg/liter (mean +/- SE) (p less than .05). In contrast, the mean serum trough concentration of furosemide remained at a plateau following the first dose (1.8 +/- 0.82 to 1.98 +/- 1.81 mg/liter), suggesting attainment of a steady state. This accumulation of furosemide following repeated doses of this diuretic, therefore, reflects the decreased plasma clearance of the drug, possibly due to contraction of its volume of distribution.