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Single-dose pharmacokinetics of imipenem in children
Insights
Pediatric pharmacokinetics of imipenem (N-formimidoyl thienamycin) show rapid distribution and elimination. A 25 mg/kg dose every 6 hours appears suitable for initiating pediatric imipenem therapy.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Metabolism
Background:
- Imipenem (N-formimidoyl thienamycin) is a broad-spectrum antibiotic.
- Understanding pediatric pharmacokinetics is crucial for safe and effective dosing.
- Limited data exists on imipenem pharmacokinetics in pediatric populations.
Purpose of the Study:
- To evaluate the single-dose pharmacokinetics of imipenem in pediatric patients.
- To compare pediatric pharmacokinetic data with adult data.
- To determine an appropriate dosing regimen for imipenem in children.
Main Methods:
- 13 pediatric patients received single doses of imipenem (10 or 25 mg/kg) with cilastatin.
- Plasma drug concentrations were measured over time.
- Pharmacokinetic parameters were calculated using a two-compartment open model.
Main Results:
- Imipenem plasma disposition followed a two-compartment model with rapid distribution (t1/2 lambda 1 = 0.18 hr) and elimination (t1/2 lambda 2 = 1.2 hr).
- Apparent volume of distribution (0.66 L/kg) and total plasma clearance (0.36 L/hr/kg) were determined.
- Pediatric pharmacokinetic parameters differed from those reported in adults.
Conclusions:
- A 25 mg/kg dose of imipenem administered every 6 hours is suggested as adequate for initiating therapy in children.
- Further pharmacokinetic simulations support this proposed pediatric dosing regimen.
- The study highlights differences in imipenem disposition between pediatric and adult patients.
Abstract:
The single-dose pharmacokinetics of imipenem (N-formimidoyl thienamycin) was evaluated in 13 pediatric patients (mean age 5.2 +/- 3.5 years). Imipenem was administered in combination with cilastatin as either a 10 mg/kg or 25 mg/kg dose (not to exceed 500 mg) over 15 minutes. Plasma disposition in children was best described by a two-compartment open model. The distribution phase was rapid (t1/2 lambda 1 = 0.18 hours) and was followed by a monoexponential elimination phase (t1/2 lambda 2 = 1.2 hours). The calculated value for the apparent volume of distribution (0.66 L/kg) was similar to that of total body water. The total plasma clearance was rapid (0.36 L/hr/kg). Direct proportionality was exhibited between administered dose and either resultant plasma concentration or area under the plasma concentration versus time curve. Comparison of imipenem plasma pharmacokinetic data derived from these children with data reported from adult subjects revealed disparities for both the apparent volume of distribution and plasma clearance. Based on preliminary pharmacokinetic simulations using parameters generated from our study, a 25.0 mg/kg dose of imipenem administered every 6 hours appears adequate for initiation of therapy in children.