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P114 Population pharmacokinetics and dosing optimization of cefepime in neonates

Objective Cefepime, a fourth-generation cephalosporin, is used in the treatment of severe nosocomial infections in neonates. Pharmacokinetics of cefepime was limited. Therefore, we aimed to study the population pharmacokinetics of cefepime and optimize cefepime regimen in preterm and term neonates. Methods Blood samples were obtained from neonates treated with cefepime using an opportunistic sampling design. Concentration of cefepime was determined by high performance liquid chromatography. Population pharmacokinetics analysis was conducted using NONMEM software. Results Sparse pharmacokinetic samples (n=100) from 85 neonatal patients were available for analysis. A one-compartment model with first-order elimination was used to describe the pharmacokinetics of cefepime. Covariate analysis showed that current weight, postmenstrual age and serum creatinine concentration had tremendous influence on pharmacokinetics of cefepime. Monte Carlo simulation indicated that current dosage regimen (30 mg/kg, q12h) was correlated with high risk of underdosing in neonates. To achieve the target rate of 70% of patients get free drug concentration above MIC during 70% of dosing interval, 30 mg/kg q8h was required for all neonates, using susceptibility breakpoint of 4 mg/L. Conclusion The population pharmacokinetics characteristics of cefepime were evaluated in neonates. Based on simulation, different dosage regimens were required depending on the postmenstrual age and pathogens. Disclosure(s) Nothing to disclose.