Related Experiment Videos
Trimethoprim pharmacokinetics in children with renal insufficiency
Insights
Trimethoprim
Area of Science:
- Pediatric Pharmacology
- Renal Medicine
- Pharmacokinetics
Background:
- Renal insufficiency impacts drug elimination in children.
- Trimethoprim pharmacokinetics require specific consideration in pediatric patients with impaired kidney function.
Purpose of the Study:
- To investigate the pharmacokinetics of trimethoprim in pediatric patients with varying degrees of renal insufficiency.
- To establish the relationship between glomerular filtration rate (GFR) and trimethoprim's elimination half-life and clearance.
Main Methods:
- Pharmacokinetic analysis of trimethoprim in 14 children (including neonates) with renal insufficiency.
- Correlation of trimethoprim half-life (t1/2) and renal clearance with measured glomerular filtration rates (GFR).
Main Results:
- Trimethoprim half-life showed a significant inverse relationship with GFR (r = -0.86, P < 0.001).
- Reduced renal clearance was the primary cause of slower trimethoprim elimination.
- Volume of distribution was often in the upper normal range, with some infants showing larger values.
Conclusions:
- Trimethoprim dosing requires adjustment in pediatric patients with renal insufficiency, particularly when GFR is below 30 ml/min/1.73 m2.
- Dose reduction should be proportional to GFR reduction, mainly by extending the dosing interval.
Abstract:
We studied the pharmacokinetics of trimethoprim in 14 children (two neonates) with renal insufficiency. They were 1 week to 16.4 years old and had glomerular filtration rates (GFR) between 10.8 to 72.3 ml/min/1.73 m2. The half-life (t1/2) of trimethoprim was inversely related to the GFR. The relation followed a power curve (correlation of t1/2 with GFR: r = -0.86; P less than 0.001). The slower elimination rate was mainly the result of lowered renal clearance of trimethoprim. The volume of distribution (Varea) was, in most patients, in the upper normal range for children. In some of the patients, chiefly infants with severe renal insufficiency, the Varea was larger than normal. In some individuals the pharmacokinetics of trimethoprim deviated from that to be expected from the GRF. We recommend reduced daily doses of trimethoprim if the GFR is less than 30 ml/min/1.73 m2. The reduction should be proportional to the reduction in GFR and primarily take the form of a prolonged dose interval.