Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Zhou, Jie; You, Xiang; Ke, Meng; Ye, Lingling; Wu, Wanhong; Huang, Pinfang; Lin, Cuihong

doi:10.1016/j.xphs.2021.02.001

Cited by 16 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, the in vivo CL R was thus calculated as Fup*GFR and nonrenal elimination was not considered during model development. 4,40 This algorithm also supported the prediction of unbound teicoplanin concentrations for therapeutic effect and that is consistent with previous research. 41 In healthy adults, the theoretical CL R of teicoplanin by filtration was 1.01 L/h, which was close to the 0.98 L/h value reported in the literature.…”

Section: Discussionsupporting

confidence: 89%

“…Given the lack of pediatric data, use of adult data and extrapolating a model to children can diminish the requirement for more stringent PK trials, and previous studies have established successful pediatric PBPK models for ertapenem and ceftazidime. 40,46 These results from model simulations and prediction are valuable in the evaluation of potential clinical benefits and safety of drug dosing in pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Lin

Chen

et al. 2021

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment-related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36-fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration-time curve was predicted to increase 1.25fold, 1.95-fold, and 2.82-fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12-hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Lin

Chen

et al. 2021

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subsequently, using the normal population as the control group, the predicted values of critical PK parameters were compared. The age group–adjusted proposed dosage for renally impaired pediatric patients was calculated by multiplying the geometric mean ratio of AUC 0‐t of the renally impaired population to the corresponding normal population by the dose in the normal population 12,13,24,25 …”

Section: Methodsmentioning

confidence: 99%

“…The age group-adjusted proposed dosage for renally impaired pediatric patients was calculated by multiplying the geometric mean ratio of AUC 0-t of the renally impaired population to the corresponding normal population by the dose in the normal population. 12,13,24,25 Pharmacodynamic Evaluation of Ceftaroline The proposed dose for renally impaired pediatric patients was evaluated to determine whether adequate exposure and efficiency were obtained. Because ceftaroline displays time-dependent killing, the PD parameter that best predicts its activity is the free time (fT) above the minimum inhibitory concentration (MIC) expressed as the percentage of the dosage interval during which the drug's serum concentration exceeds the MIC (fT>MIC).…”

Section: Prediction Of Ceftaroline Concentrations In Renally Impaired Pediatric Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Ceftaroline Dosage Optimized for Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Zhou

You

Guo

et al. 2021

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients.

show abstract

Predicting the correct dose in children: Role of computational Pediatric Physiological‐based pharmacokinetics modeling tools

Zhang

Dun

Chen

et al. 2022

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

The pharmacokinetics (PKs) and safety of medications in particular groups can be predicted using the physiologically-based pharmacokinetic (PBPK) model. Using the PBPK model may enable safe pediatric clinical trials and speed up the process of new drug research and development, especially for children, a population in which it is relatively difficult to conduct clinical trials. This review summarizes the role of pediatric PBPK (P-PBPK) modeling software in dose prediction over the past 6 years and briefly introduces the process of general P-PBPK modeling.We summarized the theories and applications of this software and discussed the application trends and future perspectives in the area. The modeling software's extensive use will undoubtedly make it easier to predict dose prediction for young patients.

show abstract

Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Cited by 16 publications

References 46 publications

Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Ceftaroline Dosage Optimized for Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Predicting the correct dose in children: Role of computational Pediatric Physiological‐based pharmacokinetics modeling tools

Contact Info

Product

Resources

About