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Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Department of Pharmacy, Texas Children’s Hospital, Houston, TX, USA

    Brady S. Moffett & Jennifer Morris

  2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Brady S. Moffett, Jennifer Morris, Flor Munoz & Ayse Akcan Arikan

  3. Department of Pharmacy, Texas Children’s Hospital – The Woodlands, 17580 Interstate 45, Conroe, TX, 77384, USA

    Brady S. Moffett

Authors
  1. Brady S. Moffett
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  2. Jennifer Morris
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Corresponding author

Correspondence to Brady S. Moffett.

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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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Appendix 1 Fat-free mass calculation

Appendix 1 Fat-free mass calculation

$$ {\mathrm{FFM}}_{\mathrm{females}}=\left[1.11+\left(\left(1-1.11\right)/\left(1+{\left(\mathrm{Age}/7.1\right)}^{-1.1}\right)\right)\right]\times \left[\left(9270\times \mathrm{WT}\right)/\left(8780+\left(244\times \mathrm{BMI}\right)\right)\right] $$
$$ {\mathrm{FFM}}_{\mathrm{males}}=\left[0.88+\left(\left(1-0.88\right)/\left(1+{\left(\mathrm{Age}/13.4\right)}^{-12.7}\right)\right)\right]\times \left[\left(9270\times \mathrm{WT}\right)/\left(6680+\left(216\times \mathrm{BMI}\right)\right)\right] $$
WT:

weight (kg)

Age:

age in years

BMI:

body mass index (kg/m2)

Table 5 Individual covariate analysis
Full size table
Table 6 Bootstrap analysis
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Moffett, B.S., Morris, J., Munoz, F. et al. Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy. Eur J Clin Pharmacol 75, 1089–1097 (2019). https://doi.org/10.1007/s00228-019-02664-7

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  • DOI: https://doi.org/10.1007/s00228-019-02664-7

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