Population pharmacokinetic model of levetiracetam in Korean neonates with seizures

作者：Jung Yun Seob; Lee Soon Min; Park Min Soo; Park Kyungsoo^*

来源：International Journal of Clinical Pharmacology and Therapeutics, 2018, 56(5): 217-223.

DOI：10.5414/CP203058

• allometry
• levetiracetam
• NONMEM
• population pharmacokinetics
• postmenstrual age

Objective: This study was conducted to develop a population pharmacoki-netic (PK) model of levetiracetam in Korean neonates with seizures. Materials and methods: Data were obtained from a retrospective study of 18 neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of Severance Children's Hospital for the period of from 2013 to 2015. Sampling and dosing times were recorded by clinical research coordinators on case report forms. Demographic factors and laboratory results were tested as potential covariates for PK parameters. Model development was performed within a mixed-effect modeling framework using NONMEM. Results: With a one-compartment model with first-order elimination chosen as a basic PK model based on theory-based allometric relationships, postmenstrual age and serum creatinine were found to have significant influences on clearance (CL). Typical parameter estimates of the final PK model obtained, evaluated at covariate medians, were 1.08 L/kg for volume of distribution (V) and 0.073 L/h/kg (= 1.23 mL/min/ kg) for CL, illustrating that V in Korean neonates is a little larger than in Western population while CL is similar. Conclusion: A population PK model of levetiracetam for Korean neonates with seizures was developed in this study. The result of this study can be used as a basis to develop an optimal dosage regimen in Korean neonates with seizures.

• 出版日期2018-5