Gentamicin Pharmacokinetics and Dosing in Neonates with Hypoxic Ischemic Encephalopathy Receiving Hypothermia

• DOI: 10.1002/phar.1263
• Publication Date: 2013-04-01T12:54:01Z
• Authors: Adam Frymoyer; Lina Meng; Sonia L. Bonifacio; Davide Verotta; B. Joseph Guglielmo
• Keywords: NONMEM; Therapeutic Drug Monitoring; Trough Concentration

Study Objective To evaluate the pharmacokinetics of gentamicin in neonates with hypoxic ischemic encephalopathy ( HIE ) receiving hypothermia and to identify an empiric dosing strategy this population that optimizes achievement target peak trough concentrations. Design Population pharmacokinetic study using retrospective medical record data. Setting Tertiary neonatal intensive care unit. Patients A total 29 full‐term diagnosed treated who received underwent therapeutic drug monitoring Measurement Main Results Patient demographics concentration data were retrospectively collected over a 2‐year period. population‐based model was developed nonlinear mixed‐effects modeling (NONMEM). Using model, Monte Carlo simulations performed probability achieving (> 6 mg/L) (< 2 concentrations for various potential regimens. one‐compartment best described available Birthweight serum creatinine significantly influenced clearance. For typical neonate (birthweight 3.3 kg, 0.9 mg/dl), clearance 0.034 L/hour/kg volume 0.52 L/kg. At 24‐hour interval, predicted could not be reliably achieved at any dose. 36‐hour dose 4–5 mg/kg is achieve more than 90% neonates. Conclusions Gentamicin decreased compared previous reports nonasphyxiated normothermic prolonged interval will needed population. Further prospective evaluation recommendation needed.