Optimizing Gentamicin Dosing in Pediatric Oncology Patients

Gentamicin is commonly used to treat Gram-negative infections in pediatrics. However, its pharmacokinetics (PK) are highly variable, particularly in oncology patients, owing to physiological changes associated with malignancy and chemotherapy. This study aimed to develop a population PK model for gentamicin in oncology pediatrics to further identify their optimal dosing strategy.

A retrospective multicenter study included pediatric patients (1 month-14 years) receiving gentamicin with therapeutic drug monitoring data available. Population PK modeling was performed, incorporating covariates such as age, body weight, fat-free mass, glomerular filtration rate (GFR) and oncology status. Monte Carlo simulations were conducted to assess the probability of target attainment for various dosing regimens based on PK/pharmacodynamic indices of peak serum concentration to minimum inhibitory concentration (Cmax/MIC ≥8) and safety threshold (trough <1 mg/L).

Data from 222 patients (98 oncology and 124 nononcology) were analyzed. A one-compartment model with linear elimination best describes gentamicin disposition. Body weight, age and GFR were identified as significant covariates influencing clearance. Oncology status did not significantly affect PK parameters. Augmented renal clearance (GFR ≥ 130 mL/min/1.73m²) was significantly more prevalent in oncology patients (33.7% vs. 21.0%; P = 0.04). Simulations indicated that for pathogens with MIC ≤ 1 mg/L, a minimum daily dose of 6 mg/kg is required to achieve a probability of target attainment ≥90% with low toxicity risk. However, for MIC = 2 mg/L, even the 10 mg/kg dose failed to attain therapeutic targets.

While oncology status has a minimal effect on gentamicin PK, the high prevalence of augmented renal clearance underscores the need for individualized dosing guided by PK modeling and therapeutic drug monitoring to ensure efficacy and minimize toxicity.