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Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children
J L Blumer1, M D Reed, G L Kearns
1Case Western Reserve University, Cleveland, Ohio, USA.
Insights
This study determined meropenem dosing for children. A 20 mg/kg dose every 8 hours is recommended to effectively treat pediatric bacterial infections.
Area of Science:
- Pharmacology
- Pediatric Infectious Diseases
Background:
- Meropenem is a broad-spectrum carbapenem antibiotic.
- Effective treatment of pediatric bacterial infections requires precise dosing.
Purpose of the Study:
- To establish meropenem dosing guidelines for pediatric patients.
- To evaluate meropenem pharmacokinetics across different pediatric age groups.
Main Methods:
- An escalating, single-dose pharmacokinetic study was conducted.
- 73 infants and children aged 2 months to 12 years were enrolled.
- Doses of 10, 20, and 40 mg/kg were administered.
Main Results:
- No significant age- or dose-dependent pharmacokinetic effects were observed.
- Key pharmacokinetic parameters (half-life, volume of distribution, clearance) were determined.
- Approximately 55% of the dose was excreted as unchanged drug in urine within 12 hours.
Conclusions:
- A meropenem dose of 20 mg/kg every 8 hours is proposed.
- This dosage is predicted to maintain plasma concentrations above the minimum inhibitory concentration for susceptible pathogens.
- No significant adverse events were reported, indicating a favorable safety profile.
Abstract:
Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.