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Kinetics of furosemide in children with chronic renal failure undergoing regular haemodialysis
Insights
Furosemide pharmacokinetics in children with chronic renal failure show a longer half-life and lower clearance. Current dosing may not require adjustment despite these changes in furosemide metabolism.
Area of Science:
- Pharmacology
- Nephrology
- Pediatrics
Background:
- Chronic renal failure (CRF) significantly alters drug pharmacokinetics.
- Pediatric CRF patients undergoing hemodialysis present unique challenges for drug management.
- Understanding furosemide disposition is crucial for effective treatment in this population.
Purpose of the Study:
- To investigate the pharmacokinetics of furosemide in children with chronic renal failure on regular hemodialysis.
- To assess the impact of chronic renal failure and hemodialysis on furosemide half-life, clearance, and protein binding.
- To determine if current furosemide dosage regimens need modification in pediatric CRF patients.
Main Methods:
- Gas-liquid chromatography was used to measure furosemide concentrations in blood and dialysis fluid.
- Pharmacokinetic parameters were determined in 7 children with CRF undergoing chronic hemodialysis.
- Two children received an intravenous dose for detailed pharmacokinetic analysis.
Main Results:
- Furosemide exhibited a prolonged half-life and significantly lower systemic and renal clearance compared to adults.
- Plasma protein binding of furosemide was reduced in some pediatric patients.
- Hemodialysis contributed minimally (less than 10%) to overall furosemide clearance.
Conclusions:
- Despite altered pharmacokinetics, including a 4-5 fold increase in half-life, current furosemide dosage schedules in pediatric CRF patients may be appropriate.
- The low contribution of hemodialysis to drug clearance suggests limited benefit from altering dialysis parameters for furosemide removal.
- Further studies may be warranted to confirm long-term efficacy and safety of current dosing.
Abstract:
Furosemide was measured by gas-liquid chromatography in blood and dialysis fluid from 7 children with chronic renal failure, undergoing regular haemodialysis. It was administered chronically, in two or three daily doses (4.2-9.4mg/kg). Two children received 1 mg/kg intravenously for determination of the pharmacokinetics. The half-life was longer than in adults and in anephric patients on haemodialysis. Systemic and renal clearance were also much lower. Plasma protein binding in 2 out of 6 cases was reduced as compared to normal adults. The data do not suggest any need to modify the present dosage schedule despite the 4-5 fold increase in the half-life of furosemide. The contribution of haemodialysis to drug clearance was minimal, and accounted for less than 10% of the total clearance.