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Single-dose pharmacokinetics of imipenem-cilastatin in neonates
Insights
Single-dose pharmacokinetics of imipenem-cilastatin in neonates showed favorable drug exposure. This antibiotic combination is safe for single-dose use in newborns, with no observed adverse effects.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Imipenem (N-formimidoyl thienamycin) is a broad-spectrum beta-lactam antibiotic.
- Cilastatin is a renal dehydropeptidase I inhibitor, co-administered to prevent imipenem degradation.
- Understanding the pharmacokinetic profile of imipenem-cilastatin in neonates is crucial for appropriate dosing and therapeutic efficacy.
Purpose of the Study:
- To evaluate the single-dose pharmacokinetics of intravenous imipenem-cilastatin in neonates.
- To determine drug concentrations in serum, urine, and cerebrospinal fluid.
- To assess the safety profile of a single dose of imipenem-cilastatin in this population.
Main Methods:
- Ten neonates (1-8 days old) received a single intravenous dose of imipenem-cilastatin (15 or 25 mg/kg).
- Serum, urine, and cerebrospinal fluid (CSF) samples were collected.
- Drug concentrations were quantified using high-pressure liquid chromatography (HPLC); pharmacokinetic parameters were analyzed using a two-compartment open model.
Main Results:
- Mean peak plasma imipenem levels at 30 min postinfusion were 55.4 and 27.2 µg/ml for 25 and 15 mg/kg doses, respectively.
- Mean elimination half-life (t1/2 beta) values were 2.1 h (25 mg/kg) and 1.8 h (15 mg/kg).
- CSF imipenem levels at 1.5 h postinfusion were 5.6 and 1.1 µg/ml (25 and 15 mg/kg), representing 10% and 4% of serum levels, respectively.
Conclusions:
- The single-dose pharmacokinetics of imipenem-cilastatin in neonates suggest adequate drug exposure.
- The calculated volume of distribution was 0.41 L/kg.
- No adverse effects were observed following a single dose, indicating good tolerability in this age group.
Abstract:
The single-dose pharmacokinetics of imipenem (N-formimidoyl thienamycin), a beta-lactam antibiotic, used in combination with cilastatin, a renal dehydropeptidase I inhibitor, were evaluated in 10 neonates 1 to 8 days of age. The imipenem-cilastatin combination was given intravenously over a 15-min period at a dose of 15 or 25 mg/kg. Drug concentrations in serum, urine, and cerebrospinal fluid (when available) were determined by high-pressure liquid chromatography, and plasma disposition of the drugs was described by a two-compartment open model. The mean peak plasma levels of imipenem 30 min postinfusion were 55.4 and 27.2 micrograms/ml, and the mean t1/2 beta values were 2.1 and 1.8 h at doses of 25 and 15 mg/kg, respectively. The calculated volume of distribution was 0.41 liters/kg. In two patients from whom cerebrospinal fluid was obtained 1.5 h postinfusion, imipenem levels were 5.6 and 1.1 micrograms/ml at doses of 25 and 15 mg/kg, respectively, representing 10 and 4% of the 1-h serum levels. No side effects attributable to a single dose of imipenem-cilastatin were noted.