Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Infants

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2018 Jan 31

PMID 29378703

Citations 11

Authors

Zhong-Ren Shi

Xing-Kai Chen

Li-Yuan Tian

Ya-Kun Wang

Gu-Ying Zhang

Lei Dong

Totsapol Jirasomprasert

Evelyne Jacqz-Aigrain

Wei Zhao

Affiliations

Soon will be listed here.

Abstract

Ceftazidime, a third-generation cephalosporin, can be used for the treatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data are limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and to define the appropriate dose to optimize ceftazidime treatment. Blood samples were collected from children treated with ceftazidime, and concentrations of the drug were quantified by high-performance liquid chromatography with UV detection (HPLC-UV). A population pharmacokinetic analysis was performed using NONMEM software version 7.2.0). Fifty-one infants age range, 0.1 to 2.0 years were included. Sparse pharmacokinetic samples = 90 were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight and creatinine clearance (CL) were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mgkg twice daily was associated with a high risk of underdosing in infants. In order to reach the target of 70% of the time that the free antimicrobial drug concentration exceeds the MIC (), 25 mg/kg every 8 h (q8h) and 50 mg/kg q8h were required for MICs of 4 and 8 mg/liter, respectively. The population pharmacokinetic characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation.

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