Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia
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PHARMACOKINETICS AND DISPOSITION
Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia Muhammad Wasim Khan 1 & Ya-Kun Wang 2 & Yue-E Wu 1 & Bo-Hao Tang 1 & Min Kan 1 & Hai-Yan Shi 3 & Yi Zheng 1 & Bao-Ping Xu 4 & A-Dong Shen 5 & Evelyne Jacqz-Aigrain 6,7 & Li-Yuan Tian 2 & Wei Zhao 1,3 Received: 12 February 2020 / Accepted: 17 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen. Methods From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained. Results The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L). Conclusion Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach. Keywords Community-acquired pneumonia . Ceftriaxone . Dosing regimen . Children
Introduction In children, community-acquired pneumonia (CAP) is one reason for the immense rate of hospital admissions [1]. The occurrence of CAP infection is 5 to 11/1000 people/year in Europe and North America in adults [2]. In the USA, the
average occurrence of CAP is about 2.5/1000 people/year in inpatient adults, in patients aged 65 to 79 years, the occurrence is 6.3/1000 people/year, and in patients 80 years old and older, the ratio of occurrence is as high as 16.4/1000 people/year [3]. According to research performed in 2013 in China, there are 16,585 CAP inpatient cases registered, among which high
Li-Yuan Tian and Wei Zhao contributed equally to this work. * Wei Zhao [email protected] 1
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No. 44, Wenhua West Road, Jinan, Shandong Province, China
2
Department of Respiratory Care, Children’s Hospital of Hebei Province affiliated to Hebei Medical University, Shijiazhuang, China
3
Department of Clinical Pharmacy, Clinical Trial Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
4
China National Clinical Research Center for Respiratory Diseases, Respiratory Department, Beijing Childr
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