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Pharmacokinetics of amikacin in cystic fibrosis: a study of bronchial diffusion
Insights
Pharmacokinetic studies in children with cystic fibrosis show amikacin plasma levels are dose-dependent. Higher doses improve bronchial diffusion, but sputum concentrations remain below the minimum inhibitory concentration (MIC) except at the highest dose.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Pulmonology
- Infectious Diseases
Background:
- Cystic fibrosis (CF) affects lung function and drug disposition.
- Amikacin is an aminoglycoside antibiotic used for bacterial infections, often in CF patients.
- Understanding amikacin's bronchial diffusion is crucial for optimizing CF treatment.
Purpose of the Study:
- To evaluate the pharmacokinetic profile and bronchial diffusion of amikacin in pediatric cystic fibrosis patients.
- To determine the relationship between amikacin dosage, plasma concentrations, and sputum penetration.
- To inform optimal amikacin dosing regimens for children with CF.
Main Methods:
- Intravenous (IV) amikacin administration in 9 children with CF (ages 3-15) and 4 healthy controls.
- Variable dosage regimens (5, 7.5, 12.5 mg/kg) were used.
- Plasma and sputum concentrations, half-life, volume of distribution, and plasma clearance were measured.
Main Results:
- Amikacin pharmacokinetic parameters (half-life, Vd, clearance) did not differ significantly between CF patients and controls.
- Peak plasma concentrations increased with dose, remaining above the minimum inhibitory concentration (MIC).
- Sputum concentrations were generally below MIC, except at the highest dose (15 mg/kg); sputum/plasma AUC ratio increased over treatment.
Conclusions:
- Amikacin exhibits predictable pharmacokinetics in pediatric CF patients.
- Higher doses are needed to achieve therapeutic amikacin concentrations in sputum.
- Findings support adjustments to amikacin dosing strategies for improved efficacy in CF lung infections.
Abstract:
36 pharmacokinetic studies of amikacin were performed to evaluate the bronchial diffusion of amikacin in 9 children with cystic fibrosis, 3 to 15 years old. Amikacin was administered i.v. according to a variable dosage regimen. Four children without cystic fibrosis were enrolled as controls. The mean half life was 1.1, the volume of distribution averaged 0.26 l/kg, and the mean plasma clearance was 131 ml/min/1.73 m2, which no differed from that of the controls. The mean peak plasma concentration was always above the MIC but its level depended on the unit dose: 18.5 mg/l, 25,95 mg/l and 31,46 mg/l for doses of 5, 7.5 and 12.5 mg/kg, respectively. Between consecutive amikacin infusions, the plasma level was above the MIC for 21% and 46% of the time after the 5 and 7.5 mg/kg doses. The maximum concentration in sputum between H1 and H2 was always below the MIC, except after 15 mg/kg. The ratio AUC sputum/AUC plasma was between 0.028 and 0.61, and it increased from the beginning to the end of the course of treatment. No side effects were observed on hearing, or vestibular and renal function. The results are used to suggest more appropriate dosing regimens.