Brady S Moffett1,2,3, Jennifer Morris4,5, Flor Munoz5, Ayse Akcan Arikan5. 1. Department of Pharmacy, Texas Children's Hospital, Houston, TX, USA. bsmoffet@texaschildrens.org. 2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. bsmoffet@texaschildrens.org. 3. Department of Pharmacy, Texas Children's Hospital - The Woodlands, 17580 Interstate 45, Conroe, TX, 77384, USA. bsmoffet@texaschildrens.org. 4. Department of Pharmacy, Texas Children's Hospital, Houston, TX, USA. 5. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Abstract
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.
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 ureanitrogen (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 ureanitrogen, 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.
Entities:
Keywords:
Dialysis; NONMEM; Pediatrics; Population pharmacokinetics; Renal replacement therapy; Vancomycin
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