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Published on: August 30, 2018
Population pharmacokinetics and dosing optimization of cefoselis in paediatric patients with haematological
Jing-Rui Liu1, Shu-Meng Fu2, Totsapol Jirasomprasert2
1Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Insights
This study optimized cefoselis dosing in pediatric cancer patients by analyzing pharmacokinetics (PK). The findings support effective cefoselis use, ensuring better treatment outcomes and safety in this vulnerable population.
Area of Science:
- Pharmacology
- Pediatric Oncology
- Infectious Diseases
Background:
- Cefoselis, a fourth-generation cephalosporin, is used for bacterial infections.
- Its pharmacokinetic (PK) profile, efficacy, and safety in pediatric patients with hematological malignancies are not well-defined.
- This uncertainty risks suboptimal dosing, leading to treatment failure or toxicity.
Purpose of the Study:
- To establish a population pharmacokinetic (PopPK) model for cefoselis in pediatric patients with hematological malignancies.
- To evaluate current cefoselis dosing regimens in this patient group.
- To optimize cefoselis dosing for improved therapeutic outcomes.
Main Methods:
- Population pharmacokinetic (PopPK) analysis using NONMEM (v7.4).
- Collected 96 blood samples from 53 pediatric patients with hematological malignancies.
- Utilized Monte Carlo simulations to assess probability of target attainment (PTA) and clinical data for efficacy and safety.
Main Results:
- A two-compartment model with zero-order input and first-order elimination best described cefoselis PK, with weight as the sole covariate.
- High PTA (>96.7%) was observed for susceptible pathogens (MIC=0.25 mg/L) at 40 mg/kg.
- Low PTA (<30.5%) was found for Pseudomonas aeruginosa (MIC=32 mg/L) at 80 mg/kg. No adverse events led to treatment discontinuation.
Conclusions:
- Established a robust PopPK model for cefoselis in pediatric patients with hematological malignancies.
- Evaluated current dosing regimens, identifying potential for optimization.
- The findings provide a basis for refined cefoselis dosing strategies in this population.
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.
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