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Pharmacokinetics of gentamicin during peritoneal dialysis in children
Insights
Gentamicin pharmacokinetics in children with chronic renal failure on peritoneal dialysis showed prolonged half-lives and variable clearance. Dosage adjustments based on serum concentrations are crucial for effective gentamicin therapy.
Area of Science:
- Pharmacology
- Nephrology
- Pediatrics
Background:
- Chronic renal failure (CRF) in children often necessitates antibiotic therapy.
- Peritoneal dialysis (PD) is a common treatment modality for pediatric CRF.
- Gentamicin is frequently used for bacterial infections but requires careful dosing due to its narrow therapeutic index.
Purpose of the Study:
- To investigate the pharmacokinetics of gentamicin in pediatric patients undergoing intermittent peritoneal dialysis.
- To compare gentamicin pharmacokinetics following intravenous (IV) and intraperitoneal (IP) administration.
- To determine the impact of PD on gentamicin elimination and identify factors influencing its serum concentrations.
Main Methods:
- Five pediatric patients with CRF on intermittent PD were studied on two occasions.
- Gentamicin was administered via IV and IP routes.
- Serum, urine, and dialysis fluid (DF) samples were collected and assayed for gentamicin concentrations.
- Pharmacokinetic parameters were analyzed using a two-compartment model.
Main Results:
- Mean gentamicin half-life was significantly prolonged (21 hours) compared to normal (2 hours).
- Peritoneal clearance averaged 4.0 ml/min/m², and renal clearance was low (1.6 ml/min/m²).
- IP administration resulted in serum concentrations averaging 42% of DF concentrations, with significant inter-patient variability.
Conclusions:
- Gentamicin pharmacokinetics in pediatric patients with renal insufficiency on PD are highly variable.
- Prolonged half-lives and altered clearance necessitate individualized dosing strategies.
- Therapeutic drug monitoring, including serum gentamicin level measurements, is essential for optimizing gentamicin therapy and minimizing toxicity in this population.
Abstract:
The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.