Related Experiment Video
Updated: Jan 27, 2026
Predicting the Effectiveness of Population Replacement Strategy Using Mathematical Modeling
Published on: July 4, 2007
Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy
Brady S Moffett1,2,3, Jennifer Morris4,5, Flor Munoz5
1Department of Pharmacy, Texas Children's Hospital, Houston, TX, USA. bsmoffet@texaschildrens.org.
Insights
Optimizing vancomycin dosing in pediatric patients on continuous veno-venous hemodiafiltration (CVVHDF) requires understanding its pharmacokinetics. Recommended doses are 40-50 mg/kg/day, divided every 8-12 hours, with regular monitoring.
Area of Science:
- Pharmacology
- Nephrology
- Pediatrics
Background:
- Dosing vancomycin in pediatric patients undergoing continuous veno-venous hemodiafiltration (CVVHDF) presents significant challenges.
- Understanding vancomycin pharmacokinetics is crucial for achieving target serum concentrations in this population.
Purpose of the Study:
- To characterize vancomycin pharmacokinetics in pediatric patients on CVVHDF.
- To identify optimal dosing regimens to achieve target vancomycin serum concentrations and AUC0-24:MIC ratios.
Main Methods:
- A population pharmacokinetic analysis was conducted using NONMEM 7.2 and PDx-Pop 5.2.
- Data included patient demographics, vancomycin doses and concentrations, CVVHDF parameters, and laboratory values.
- Simulations were performed to evaluate different dosing strategies.
Main Results:
- Vancomycin pharmacokinetics were best described by a two-compartment model with fat-free mass as a covariate.
- Key covariates influencing clearance included serum creatinine, blood urea nitrogen, dialysate flow rate, and ultrafiltration rate.
- Simulations indicated that doses of 40-50 mg/kg/day divided every 8-12 hours maximized target attainment.
Conclusions:
- Fat-free mass, serum creatinine, blood urea nitrogen, dialysate flow rate, and ultrafiltration rate are significant factors in vancomycin pharmacokinetics for pediatric CVVHDF patients.
- A vancomycin dosage of 40-50 mg/kg/day, based on fat-free mass and administered every 8-12 hours, is recommended.
- Frequent monitoring of vancomycin serum concentrations is advised for this patient group.
Background And Objectives:
Dosing of vancomycin in pediatric patients undergoing continuous venous-venous hemodiafiltration (CVVHDF) is challenging. Characterization of vancomycin pharmacokinetics can assist with dosing and attainment of goal serum concentrations.
Design, Setting, Participants, And Measurements:
Patients less than 19 years of age who received vancomycin and had post-dose vancomycin concentrations while undergoing CVVHDF were identified. Data collection included the following: patient demographics, vancomycin dosing and serum concentrations, CVVHDF variables, serum creatinine (SCR), blood urea nitrogen (BUN), albumin, hematocrit, and urine output. Fat-free mass was calculated. Data were summarized with descriptive statistical methods, and population pharmacokinetic analysis was performed with NONMEM 7.2 and PDx-Pop 5.2. Simulation was performed to identify dosing regimens with the highest percentage of goal serum concentration < 20 mg/L and AUC0-24:MIC ≥ 400 attainment.
Results:
A total of 138 patients met study criteria (45.6% male, median age 4.9 years (IQR (1.0, 14.5))). Mean vancomycin dose was 14.3 ± 1.6 mg/kg/dose (19.5 ± 3.0 mg/kg/dose by FFM). Patients had a median of six (IQR 2, 12) vancomycin serum concentrations sampled 13.6 ± 8.4 h after the dose, and the mean vancomycin serum concentration was 11.3 ± 3.4 mg/L. Vancomycin pharmacokinetics were characterized by a two-compartment model with allometric scaling on fat-free mass and significant covariates of SCR, BUN, dialysate flow rate, and ultrafiltration rate on clearance. Simulation identified doses of 40-50 mg/kg/day that divided every 8-12 h had the highest percentage of patients with a serum concentration < 20 mg/L and an AUC0-24:MIC ≥ 400.
Conclusions:
Vancomycin pharmacokinetics are characterized by fat-free mass, serum creatinine, blood urea nitrogen, dialysate flow rate, and ultrafiltration rate in the pediatric CVVHDF population. Dosing of 40-50 mg/kg/day on fat-free mass divided every 8-12 h with frequent vancomycin serum sampling is recommended.
Related Concept Videos
01:30Continuous Renal Replacement Therapy
01:26Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy
01:12Analysis of Population Pharmacokinetic Data
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism