Population pharmacokinetics and dosing optimization of cefoselis in paediatric patients with haematological malignancies.

Abstract

BACKGROUND: Cefoselis is a fourth-generation cephalosporin primarily indicated for infections caused by susceptible bacteria. The pharmacokinetic (PK) characteristics, efficacy and safety of cefoselis in paediatric patients with haematological malignancies remain unclear, posing a risk of suboptimal exposure and associated therapeutic failure or toxicity. Therefore, we studied cefoselis pharmacokinetics (PK) to optimize dosing in paediatric patients with haematological malignancies. METHODS: Blood samples were collected from paediatric patients with haematological malignancies. A population PK (PopPK) analysis was performed using NONMEM (v7.4). Monte Carlo simulations were used to evaluate current dosing regimens by calculating the PTA. Pharmacodynamic target was defined as unbound plasma concentrations above the MIC throughout the entire dosing interval. Clinical efficacy and safety data were collected. RESULTS: A total of 96 samples from 53 patients were collected. A two-compartment model with zero-order input and first-order elimination best described the PK of cefoselis after IV administration. Weight was the only covariate that affected PK. Monte Carlo simulations showed that the PTA was more than 96.7% for susceptible pathogens (MIC = 0.25 mg/L) at 40 mg/kg, and less than 30.5% for Pseudomonas aeruginosa (MIC = 32 mg/L) at 80 mg/kg. A total of 39 patients had body temperatures below 37.3°C after 3 ± 1 days of cefoselis treatment (with a median baseline temperature of 38.5°C). There were no adverse events leading to discontinuation. CONCLUSIONS: A PopPK model of cefoselis in paediatric patients with haematological malignancies was established and the dosing regimens were evaluated.