Population pharmacokinetics and dosing optimization of mezlocillin in neonates and young infants

Jing Zhou, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Li Jiang, Department of Pediatrics, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China.
Zhi-Ling Zhang, Department of Pediatrics, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China.
Zhao-Rui Wang, Department of Pediatrics, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China.
Yan-Xiu Zhang, Department of Pediatrics, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China.
Xu Lin, Department of Pediatrics, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, 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, 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, China.
Zi-Xuan Guo, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Jing-Jing Yang, Department of Pharmacy, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China.
John Van Den Anker, Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
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, 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, China.

Document Type

Journal Article

Publication Date

6-4-2022

Journal

The Journal of antimicrobial chemotherapy

DOI

10.1093/jac/dkac176

Abstract

OBJECTIVES: Mezlocillin is used in the treatment of neonatal infectious diseases. However, due to the absence of population pharmacokinetic studies in neonates and young infants, dosing regimens differ considerably in clinical practice. Hence, this study aimed to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin. METHODS: A prospective, open-label pharmacokinetic study of mezlocillin was carried out in newborns. Blood samples were collected using an opportunistic sampling method. HPLC was used to measure the plasma drug concentrations. A population pharmacokinetic model was developed using NONMEM software. RESULTS: Ninety-five blood samples from 48 neonates and young infants were included. The ranges of postmenstrual age and birth weight were 29-40 weeks and 1200-4000 g, respectively, including term and preterm infants. A two-compartment model with first-order elimination was developed to describe the population pharmacokinetics of mezlocillin. Postmenstrual age, current weight and serum creatinine concentration were the most important covariates. Monte Carlo simulation results indicated that the current dose of 50 mg/kg q12h resulted in 89.2% of patients achieving the therapeutic target, when the MIC of 4 mg/L was used as the breakpoint. When increasing the dosing frequency to q8h, a dose of 20 mg/kg resulted in 74.3% of patients achieving the therapeutic target. CONCLUSIONS: A population pharmacokinetic model of mezlocillin in neonates and young infants was established. Optimal dosing regimens based on this model were provided for use in neonatal infections.

Department

Pediatrics

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