Pharmacokinetic Variability of Amikacin After Once-Daily and Twice-Daily Dosing Regimen in Full-Term Neonates

Abstract

The purpose of the study was to compare peak (C-peak) and trough (C-trough) amikacin levels after twice-daily (TD) or once-daily dosing (OD) in full-term neonates. Additionally, the study aimed to address amikacin pharmacokinetics and its variability. Data included 31 patients born on term. Amikacin daily dose was 15 or 20 mg/kg depending on the neonate's age. Patients randomly received amikacin every 12 or 24 h. In all patients corresponding C-peak and C-trough were taken. Volume of distribution (Vd), clearance (CL) and half-life (t(1/2)) were calculated. Mean C-peak of 21.79 mu g/ml in the TD group was statistically different from C-peak of 36.39 mu g/ml in the OD group. Average C-trough in TD (5.67 mu g/ml) was statistically different from the corresponding 3.99 mu g/ml in the OD group. Mean amikacin Vd, CL, and tin were 0.78 +/- 0.38 l/kg, 86.99 +/- 48.22 ml/h.kg, and 6.81 +/- 2.51 h, respectively. High interindividual pharmacokinetic variability was observed. Further analysis showed that neonatal age contributed to the pharmacokinetic parameters' values. Statistically significant difference in CL and tin was observed between patients age lt = 2 and > 2 days on therapy initiation. As expected, amikacin given OD achieved higher C-peak and lower C-trough than TD. Based on the results, observed variability in amikacin pharmacokinetics was possibly due to the renal maturation process.