Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance

Frontiers in Pharmacology

John van den Anker¹  Xin-Mei Yang²  Hai-Yan Shi²  Bin Du³  Yue Zhou³  Bo-Hao Tang³  Guo-Xiang Hao³  Wei Zhao³  Yue-E Wu³  Bu-Fan Yao³  Yi Zheng⁴  Dian-Ping You⁷ 

[1] Physiology, Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States;Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China;Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital, University of Basel, Basel, Switzerland;;Departments of Pediatrics, Pharmacology &Division of Clinical Pharmacology, Children’s National Medical Center, Washington, DC, United States;Pediatric Research Institute, Children’s Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, China;

关键词: cefathiamidine;    pharmacokinetics;    dosing;    infants;    augmented renal clearance;   

DOI  :  10.3389/fphar.2021.630047

来源: DOAJ

【 摘 要 】

Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine.Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program.Results: The data (n = 36) from 20 infants (age range, 0.35–1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09–0.29) L/h/kg and 0.34 (0.24–0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively.Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.

【 授权许可】

Unknown