Prediction of gentamicin peak and trough concentrations from six extended-interval dosing protocols for neonates

Abstract

The ability of six extended-interval gentamicin dosing protocols to achieve desired peak and trough concentrations in neonates was evaluated using simulated calculations based on pooled patient data. The demographic and pharmacokinetic data of 293 neonates age one week or less from three previously published studies were pooled and applied in each of six published protocols. The data collected, including weight, dosage, dosing interval, and measured serum or plasma gentamicin concentrations, were used to determine gentamicin clearance, elimination-rate constant, and distribution volume. Peak and trough gentamicin concentrations were calculated and compared with several therapeutic ranges that aim to achieve high peak concentrations for maximum efficacy and low trough concentrations for minimum toxicity. All protocols resulted in more than 95% of peak concentrations exceeding 5 mg/L. Peaks exceeded 10 mg/L in 26-42% of the simulations. Most of the protocols resulted in high trough concentrations (0.5-1.5 mg/L). Trough concentrations were below 1 mg/L in 51-83% of the simulations. Simulated calculations based on pooled patient data found that six gentamicin dosing protocols for neonates would likely yield acceptable peak concentrations and a trough concentration of < or = 1 mg/L for at least 50% of patients. It may be sufficient to monitor only the trough concentrations when applying these protocols.