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

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 <= 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.