Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy

Eur J Clin Pharmacol. 2019 Aug;75(8):1089-1097. doi: 10.1007/s00228-019-02664-7. Epub 2019 Apr 1.


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.

Keywords: Dialysis; NONMEM; Pediatrics; Population pharmacokinetics; Renal replacement therapy; Vancomycin.

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Child
  • Child, Preschool
  • Continuous Renal Replacement Therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Retrospective Studies
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacokinetics*


  • Anti-Bacterial Agents
  • Vancomycin