Pharmacokinetics of amikacin in cystic fibrosis: A study of bronchial diffusion

Summary

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.