Eight years' experience of an extended-interval dosing protocol for gentamicin in neonates

Area of Science:

• Neonatal pharmacology
• Pharmacokinetics and pharmacodynamics
• Therapeutic drug monitoring

Background:

• Gentamicin dosing in neonates in Christchurch utilizes a locally developed extended-interval protocol since 2000.
• All dosing data are systematically recorded in a dedicated database for analysis.

Purpose of the Study:

• Analyze existing gentamicin dosing data to assess achievement of target C(max), C(min), and AUC values in neonates.
• Utilize pharmacokinetic parameters to simulate and evaluate novel gentamicin dosing protocols.

Main Methods:

• Comparison of measured C(max), C(min), and AUC against established therapeutic targets.
• Estimation of gentamicin clearance (CL), volume of distribution (V), and half-life (t(1/2)).
• Simulation and comparative analysis of new predictive dosing protocols against the established protocol.

Main Results:

• Analysis of 1053 gentamicin doses revealed 84% achieved target C(max) (>10 mg/L), 77% target C(min) (<1 mg/L), and 63% target AUC (80-125%).
• Prolonging gentamicin dosing intervals significantly improved C(max) and C(min) achievement, whereas altering predictive equations showed no improvement.
• A novel volume-based model demonstrated effectiveness, particularly for neonates receiving a single dose, with weight-dependent changes in CL, V, and t(1/2).

Conclusions:

• Extended gentamicin dosing intervals enhance the achievement of target C(max) and C(min) concentrations.
• Revising the dosing equation did not improve therapeutic outcomes; however, a volume-based model presents a viable alternative for initial gentamicin dosing in neonates.