Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy
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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.
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.
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.
KeywordsVancomycin Dialysis Renal replacement therapy Population pharmacokinetics Pediatrics NONMEM
Compliance with ethical standards
Institutional review board approval from Baylor College of Medicine and affiliated institutions was obtained
Conflict of interest
The authors are currently receiving NIH funding for a prospective population pharmacokinetic trial of vancomycin in pediatrics.
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