A hybrid PK/PD index for gentamicin dosing in premature neonates: a Monte Carlo simulation study

Gentamicindosing in premature neonates remains challenging due to developmental pharmacokinetic variability and augmented renal clearance. Conventional PK/PD targets such as Cmax/MIC and AUC/MIC capture distinct pharmacodynamic dimensions but fail to integrate efficacy and toxicity simultaneously (Craig 1998; Sime and Roberts 2020). A Monte Carlo simulation of 3000 premature neonates was conducted using published pharmacokinetic parameters (Germovsek et al. 2019; Smith et al. 2011). A Hybrid PK/PD Index (H-index) integrating peak exposure, cumulative exposure, and toxicity constraints was evaluated across clinically relevant MIC values (0.5-2 mg/L). The H-index demonstrated improved joint probability of target attainment (PTA) compared with standard dosing, with enhanced robustness across MIC variability and reduced exposure dispersion. At MIC 2 mg/L, PTA increased from 40 to 65%. The proposed Hybrid PK/PD index (H-index) provides a conceptually integrated framework for optimizing gentamicin dosing in premature neonates under simulated conditions. While these in silico findings suggest enhanced target attainment, prospective clinical validation in real-world neonatal cohorts is warranted.