Is fat-free mass-based gentamicin dosing regimen preferable than whole-body weight in neonates?

Importance:Body fluid dynamics and renal maturation status vary during the neonatal period.We hypothesized that differences in peak and trough gentamicin concentrations could be expected.Objective:To predict the peak and trough gentamicin concentrations in critically ill neonates and to predict the changes in the predicted peak plasma concentrations of gentamicin following fat-free mass dosing.Methods:Critically ill neonates that received gentamicin and have gentamicin concentration measured were recruited.Fat mass was estimated using skinfold thicknesses.Changes in the peak plasma concentrations(Cmax)using whole-body weight(estimated using the current dosing regimen)and predicted concentrations following the fat-free mass-based dosing were the outcome measures.Results:Eighty-nine critically ill neonates were recruited.Sub-therapeutic Cmax was estimated using the current dosing regimen in 32.6%,and 22.5%neonates following the first and second doses of gentamicin.Preterm neonates had significantly higher fat mass compared to term neonates.All except one had Cmax above 12μg/ml after the first dose and all had after the second gentamicin dose following the predicted fat-free massbased gentamicin dosing.The recommended doses are as follows:extreme preterm:7.95 mg/kg every 48 h;very preterm:7.30 mg/kg every 36-48 h;late preterm:5.90 mg/kg every 36-48 h;and term neonates at 5.10 mg/kg every 24 h.Interpretation:Fat-free mass dosing may be considered for obtaining optimal therapeutic effects in the neonatal population.