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

Abstract

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 mg/ml in the TD group was statistically different from C peak of 36.39 mg/ml in the OD group. Average C trough in TD (5.67 mg/ml) was statistically different from the corresponding 3.99 mg/ml in the OD group. Mean amikacin Vd, CL, and t 1/2 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 t 1/2 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.