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Kinetic parameters of amikacin in cystic fibrosis children
B Grenier1, E Autret, S Marchand
1Centre de Pédiatrie, CHRU, Tours.
Insights
This study found that amikacin plasma pharmacokinetics are similar in children with and without cystic fibrosis (CF). However, amikacin sputum concentrations in CF patients did not reach levels effective against Pseudomonas aeruginosa, suggesting a need for optimized dosing regimens.
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Medicine
- Infectious Diseases
Background:
- Cystic Fibrosis (CF) is a genetic disorder affecting multiple organs, particularly the lungs, leading to chronic infections.
- Amikacin, an aminoglycoside antibiotic, is used to treat bacterial infections, including those caused by Pseudomonas aeruginosa in CF patients.
- Understanding amikacin pharmacokinetics and achieving therapeutic concentrations in CF patients is crucial for effective treatment.
Purpose of the Study:
- To investigate and compare the plasma pharmacokinetics of amikacin in pediatric patients with and without cystic fibrosis.
- To assess amikacin concentrations in the sputum of CF children and evaluate their effectiveness against Pseudomonas aeruginosa.
- To determine an optimal intravenous dosage regimen for amikacin in CF pediatric patients.
Main Methods:
- Conducted kinetic studies in 9 CF children (3-15 years) and 4 non-CF children (1-12 years).
- Administered amikacin intravenously (5-12.5 mg/kg) over 0.5-1.0 hour, 3-4 times daily.
- Measured amikacin plasma concentrations in all children and sputum concentrations in CF patients using fluorescent polarization (TDX Abbott).
Main Results:
- Plasma pharmacokinetic parameters (t1/2, Vd, clearance) did not significantly differ between CF and non-CF children.
- Amikacin dosage did not affect pharmacokinetic parameters; peak plasma concentrations ranged from 19 to 43.8 mg/l.
- Sputum amikacin levels in CF children consistently remained below the average Minimum Inhibitory Concentration (MIC) of 4 mg/l for Pseudomonas aeruginosa.
Conclusions:
- Amikacin exhibits similar plasma pharmacokinetics in pediatric CF and non-CF populations.
- Achieving effective amikacin concentrations in the sputum of CF patients is challenging with standard dosing.
- An optimized intravenous dosage regimen of 7.5-8 mg/kg or 225-240 mg/m2, administered over 1 hour thrice daily, is recommended for CF children.
Abstract:
35 kinetic studies have been performed, in nine CF children three to 15 years old; six kinetic studies were performed in four non-CF children, one to 12 years old. The dosage was 5 to 12.5 mg/kg, i.v. during 0.5 to 1.0 h, three to four times per day. Amikacin concentrations were measured in the plasma of all children, and in the sputum of CF-patients, by fluorescent polarization (TDX Abbott). The pharmacokinetic parameters in the plasma did not differ significantly in both groups of patients. In CF children t1/2 = 0.94 h (SD = 0.25 h), Vd (area) = 0.257 l/kg (SD = 0.06 l/kg), total body clearance = 130.7 ml/min/1.73 m2 (SD = 32.4 ml/min/1.73 m2). In non-CF children t1/2 = 0.83 h (SD = 0.15 h), Vd (area) = 0.265 l/kg (SD = 0.04 l/kg) and clearance = 155 ml/min/1.73 m2 (SD = 17.4 ml/min/1.73 m2). The parameters were not affected by the dosage of amikacin. The peak plasma concentrations ranged from 19 to 43.8 mg/l. Amikacin peak level in the sputum of CF children never reached the average MIC (4 mg/l) of Pseudomonas aeruginosa strains isolated in these patients. Amikacin concentration in the sputum reached its highest value about 2 h after the completion of i.v. infusion and was directly related to the peak plasma concentration. According to these parameters, the best dosage regimen appeared to be 7.5 to 8 mg/kg or 225 to 240 mg/m2 administered intravenously in 1.0 h, three times per day.