Analysis of Gentamicin Extended Interval Dosing Protocols in a Neonatal Population

Abstract

OBJECTIVES: The purpose of this study was to analyze various published gentamicin dosing protocols in a neonate population to determine the percentage of patients that fell within defined concentration ranges, and determine which protocol was the most efficient at being within the desired concentration ranges. METHODS: Data from three published studies were used to create a database of 331 neonates who were up to seven days old and received gentamicin. Pharmacokinetic data was obtained and applied to specific dosing protocols from six published studies. The protocols were used to simulate peak and trough concentrations for each neonate. Desired trough concentrations include < 0.5 mg/L or < 1 mg/L and peak concentrations within 7-10 mg/L. Results were analyzed for frequency of achieving pre-specified concentration ranges based on dosing protocols from the study. RESULTS: The Begg protocol was adjusted for a desired Cmax of 8.5 mg/L and an estimated volume of distribution based on weight and was found to be the most efficient at achieving the highest percentage of patients achieving peaks of 7-10 mg/L and a trough of < 1 mg/L and < 0.5 mg/L, 63.0% and 61.5%, respectively. Also, other protocols which adjusted the dose based primarily on weight or gestational age such as the Fullas, Blackmer and Darmstadt protocols frequently achieved their desired trough however the average peak varied significantly, and was higher than the pre-specified concentration range. CONCLUSION: Achieving acceptable concentration ranges was suboptimal with much variability between each protocol requiring therapeutic drug monitoring and adjusting accordingly until a more efficient protocol is developed for this patient population.