Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis

Yue-E Wu, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Chen Kou, Department of Neonatology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100020, China.
Xue Li, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Bo-Hao Tang, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Bu-Fan Yao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Guo-Xiang Hao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Yi Zheng, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
John van den Anker, Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC 20010, USA.
Dian-Ping You, Pediatric Research Institute, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang 050000, China.
A-Dong Shen, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Wei Zhao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

Document Type

Journal Article

Publication Date

12-19-2022

Journal

Children (Basel, Switzerland)

Volume

9

Issue

12

DOI

10.3390/children9121998

Keywords

meropenem; neonates; population pharmacokinetics–pharmacodynamics; young infants

Abstract

The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic-pharmacodynamic analysis in Chinese newborns with the goal to optimize meropenem dosing regimens for LOS therapy. An opportunistic sampling strategy was used to collect meropenem samples, followed by model building and validation. A Monte Carlo simulation was performed to show the probability of target attainment (PTA) for various dosages. The information from 78 newborns (postmenstrual age: 27.4-46.1 weeks) was compiled and had a good fit to a 1-compartment model that had first order elimination. The median (range) values of estimated weight-normalized volume of distribution (V)and clearance (CL) were 0.60 (0.51-0.69) L/kg and 0.16 (0.04-0.51) L/h/kg, respectively. Covariate analysis revealed that postnatal age (PNA), gestational age (GA) and current weight (CW) were the most important factors in describing meropenem PK. Simulation results showed for LOS with a minimal inhibitory concentration (MIC) of 8 mg/L, the doses of 30 mg/kg 3 times daily (TID) as a 1-h infusion for newborns with GA ≤ 37 weeks and 40 mg/kg TID as a 3-h infusion for those with GA > 37 weeks were optimal, with PTA of 71.71% and 75.08%, respectively. In conclusion, we proposed an evidence-based dosing regimen of meropenem for LOS in Chinese newborns by using the population pharmacokinetic-pharmacodynamic analysis, based on domestic common pathogens and their susceptibility patterns.

Department

Pediatrics

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