Population pharmacokinetics and dosing optimization of cefathiamidine in children with hematologic infection

Abstract

PurposeCefathiamidine, a first-generation cephalosporin, has approval from the China Food and Drug Administration for the treatment of infections caused by susceptible bacteria in both adults and children. As pharmacokinetic data are limited in the pediatric population, we aimed to evaluate the population pharmacokinetics of cefathiamidine in children and to define the appropriate dose in order to optimize cefathiamidine treatment.MethodsBlood samples were collected from children treated with cefathiamidine, and concentrations were quantified by high-performance liquid chromatography and tandem mass spectrometry. Population pharmacokinetic analysis was conducted using NONMEM software.ResultsFifty-four children (age range: 2.0–11.8 years) were included. Sparse pharmacokinetic samples (n=120) were available for analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that bodyweight had a significant impact on cefathiamidine pharmacokinetics. Monte Carlo simulation demonstrated that the currently used dosing regimen of 100 mg/kg/day q12h was associated with a high risk of underdosing in pediatric patients. To reach the target 70% fT>MIC, a dose of 100 mg/kg/day cefathiamidine q6h is required for effective treatment against Haemophilus influenzae.ConclusionA population pharmacokinetics model of cefathiamidine in children with hematologic disease was established. A dosing regimen of 100 mg/kg/day cefathiamidine q6h should be used in clinical practice against H. influenza infections.

Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance

“…The estimated CL (0.09–0.29 L/h/kg) in this study is different from the CL value (0.05–0.43 L/h/kg) in children reported previously. ( Zhi et al, 2018 ). This difference is likely due to the effect of the age groups of infants and children on CL.…”

“…Considering the balance between maximum efficacy, minimum toxicity and reduction of resistance, the following pharmacokinetic-pharmacodynamic target was chosen: 70% of patients attained the target of 70% fT MIC ( Cohen-Wolkowiez et al, 2012 ; Zhi et al, 2018 ; Shi et al, 2020 ). A fixed unbound fraction of 77% was used to calculate fT MIC in this study ( Tze-ying et al, 1979 ).…”

“…In critically ill children, standard antibiotic dosing may not achieve optimal exposure due to this ARC. Nevertheless, dose optimization for pediatric patients with ARC is scarce due to a lack of PK studies; only one study has previously been reported in children with ARC, aged 2.0–11.8 years ( Zhi et al, 2018 ). To date, the pharmacokinetics of cefathiamidine are lacking in infants with ARC.…”

Ultrasound-assisted micellar cleanup coupled with large-volume-injection enrichment for the analysis of polar drugs in blood and zebrafish samples

“…Cefathiamidine, a first-generation cephalosporin, is one of the most frequently prescribed antimicrobial drugs in Chinese hospitals [34] . Due to augmented renal clearance (ARC) or severe renal impairment (RI), standard dosing might lead to underexposure or overdose in children and critically ill patients [35] , [36] , resulting in failed treatments and adverse reactions. TDM and toxicology studies of cefathiamidine are essential for successful clinical treatment, and hence the method developed in this work was applied to the analysis of cefathiamidine in real positive samples.…”