The pharmacokinetics of amikacin in critically ill adult and paediatric patients: comparison of once- versus twice-daily dosing regimens

Abstract

The pharmacokinetic profile of amikacin was analysed by a two-compartment model in 100 critically-ill adult and paediatric patients with normal renal function. In addition the serum amikacin levels in 200 patients randomized to receive a once- or twice-daily dosing regimen are reported. The mean volume of distribution (Vdt) was 0.33 l/kg in the adult patients, 0.50 l/kg in patients 6 to 12 months of age and 0.58 l/kg in patients less than 6 months old. The elimination half-life was prolonged, being 3.45, 2.86 and 5.02 h for the respective age groups (normal 2 h). The clearances dose/AUC) were 0.051, 0.068 and 0.063 l/h/kg respectively. Within each group of patients there was a large variation in the pharmacokinetic parameters, with the Vdt varying by a factor of 6 and the elimination half-life by a factor of 10. All patients receiving a once-daily dose of amikacin had therapeutic peak concentrations. In comparison, therapeutic concentrations were achieved in only 48% of adult and 44% of the paediatric patients receiving the twice-daily dosing regimen. Furthermore the amikacin trough concentrations were significantly higher in the patients who received a divided daily dose. As a consequence of the pharmacokinetic profile of amikacin in critically ill patients a once-daily dosing regimen may be more effective and less toxic than the conventional twice-daily dosing regimen.