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Pharmacokinetics of single daily dose gentamicin in children with cancer
S M Shankar1, R K Jew, B M Bickert
1Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, USA.
Insights
A single daily dose of 7 mg/kg gentamicin achieved adequate peak serum concentrations in pediatric cancer patients. However, younger children (under 5) had lower gentamicin levels than older children.
Area of Science:
- Pharmacology
- Pediatric Oncology
- Infectious Diseases
Background:
- Gentamicin is a crucial antibiotic for treating serious infections in pediatric cancer patients.
- Optimizing gentamicin dosing is essential to maximize efficacy and minimize toxicity.
- Single daily dose (SDD) regimens are often preferred for convenience and potentially improved outcomes.
Purpose of the Study:
- To evaluate the pharmacokinetics of single daily dose (SDD) gentamicin in children with cancer.
- To determine if a 7 mg/kg SDD of gentamicin achieves therapeutic peak serum concentrations.
- To compare gentamicin concentrations between different age groups in pediatric cancer patients.
Main Methods:
- Prospective measurement of serum gentamicin concentrations at various time points (0.5, 8, 16, 24 hours) after SDD.
- Two dosing regimens were studied: 6 mg/kg and 7 mg/kg, with the latter being the focus for pharmacokinetic analysis.
- Analysis included peak (0.5-hour) and trough (12-hour) concentrations in 54 pediatric cancer patients during 73 febrile episodes.
Main Results:
- The mean peak serum gentamicin concentration after a 7 mg/kg SDD was 17.2 +/- 3.9 microg/mL, aiming for 15-20 microg/mL.
- Children younger than 5 years achieved significantly lower peak concentrations (16.1 microg/mL) compared to older children (18.2 microg/mL; P = 0.02).
- Therapeutic peak concentrations were achieved in 67% of younger children and 84% of older children.
Conclusions:
- A single daily dose of 7 mg/kg gentamicin is effective in achieving adequate peak serum concentrations in pediatric cancer patients.
- Age is a significant factor, with younger children (<5 years) requiring consideration for dose adjustments due to lower achieved concentrations.
- This dosing strategy supports effective gentamicin therapy in this vulnerable population, with age-specific monitoring recommended.
Purpose:
To study the pharmacokinetics of single daily dose (SDD) gentamicin in children with cancer.
Methods:
Serum concentrations of gentamicin were prospectively measured at 0.5, 8, 16, and 24 hours after a single daily dose of gentamicin 6 mg/kg, given as a 30-minute infusion in 18 febrile children with cancer and a central venous catheter. Then the peak (0.5-hour) and 12-hour serum concentrations of gentamicin were prospectively measured after a SDD of 7 mg/kg during 73 febrile episodes in 54 pediatric cancer patients with suspected infections. The aim was to achieve a peak serum concentration of 15 to 20 microg/mL 10 times the minimum inhibitory concentration (MIC) for sensitive Pseudomonas strains, resulting in good bactericidal activity and a long post-antibiotic effect (PAE) after a SDD of gentamicin.
Results:
The mean serum peak gentamicin concentration 30 minutes after the end of the infusion of 6 mg/kg was 13.3 +/- 4.0 microg/mL. The mean serum concentration 16 hours after the infusion was 0.3 +/- 0.2 microg/mL. The mean peak and 12-hour serum concentration after SDD of 7 mg/kg was 17.2 +/- 3.9 microg/mL and 0.9 +/- 0.7 microg/mL, respectively. The mean peak serum concentration after SDD of 7 mg/kg in children younger than 5 years of age (16.1 +/- 3.5 microg/mL ) was significantly lower than that of children over 5 years of age (18.2 +/- 3.9 microg/mL; P = 0.02). The desired peak serum concentration was achieved in 67% of children younger and 84% of those older than 5 years of age.
Conclusion:
Adequate peak serum concentrations of gentamicin in children may be obtained with a SDD of 7 mg/kg. Children younger than 5 years of age achieve lower peak serum gentamicin concentration after SDD of 7 mg/kg than those older than 5 years.