Population pharmacokinetics of cefotaxime in patients with early neonatal pneumonia

Objective: This study aimed to develop a population pharmacokinetic model of cefotaxime for early neonatal pneumonia patients (postnatal age ≤ 7 days) and optimize dosage regimens to guide personalized treatment. Methods: Opportunistic blood sampling was utilized to collect samples from newborns. The model was developed using nonlinear mixed effects modeling software, enabling the determination of pharmacokinetic parameters and the completion of dose simulations for practical application. Results: A total of 51 newborns were included, and 94 blood samples of cefotaxime were collected, with the concentration ranging from 6.9 to 383.2 μg/ml. The findings indicated that a two-compartment model was most appropriate for describing the pharmacokinetics of cefotaxime in this population. Covariate analysis revealed significant influences of current body weight and age on the pharmacokinetic parameters. The median (range) weight-normalized clearance of cefotaxime was 0.08 (0.04-0.15) L/h/kg, and the median (range) values for the central and peripheral compartment volumes were 0.13 (0.10-0.16) L/kg and 0.19 (0.16-0.24) L/kg, respectively. Monte Carlo simulation results indicated that for these neonates, when the MIC was 2 μg/mL, the original dosing regimen (50.0 mg/kg, every 12 hours) achieved 100% f T _>MIC in over 90% of the neonates. Moreover, for neonates weighing ≤ 2.5 kg, reducing the dose to 25.0 mg/kg still met the target. Conclusion: The population pharmacokinetic model developed in this study provides valuable insights for the management of cefotaxime in neonates with pneumonia. This study supports the necessity of weight based personalized dosing regimens to achieve optimal treatment levels.