Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children

Area of Science:

• Pharmacology
• Pediatric Pharmacokinetics
• Antibiotic Dosing

Background:

• Individualized dosing of latamoxef in pediatric patients requires population pharmacokinetic models.
• Understanding latamoxef's R- and S-epimers is crucial for accurate therapeutic management.

Purpose of the Study:

• To establish population pharmacokinetic (PPK) models for latamoxef and its epimers in pediatric patients.
• To provide data for guiding individualized latamoxef administration in children.
• To identify covariates influencing latamoxef pharmacokinetics.

Main Methods:

• Developed three PPK models for latamoxef and its R- and S-epimers in 145 pediatric patients (0.08-10.58 years).
• Evaluated model stability and predictive ability using goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors.
• Utilized a two-compartment model with first-order elimination for total latamoxef pharmacokinetics.

Main Results:

• Established population typical values for latamoxef: V1=4.84 L, V2=16.18 L, CL=1.00 L/h, Q=0.97 L/h.
• R-epimer exhibited a higher apparent volume of distribution and lower clearance compared to the S-epimer.
• Body surface area (BSA) was identified as the most significant covariate affecting volume of distribution (V), clearance (CL), and inter-compartmental clearance (Q).

Conclusions:

• BSA is a critical factor for adjusting latamoxef dosage in pediatric patients.
• BSA-normalized dosing recommendations are provided for effective therapeutic targeting.
• This study supports optimized latamoxef administration in children based on individual BSA.