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Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration

INTRODUCTION: Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in thi...

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Autores principales: Chung, Erin, Tjon, James A., Nemec, Rosaleen M., Nalli, Nadya, Harvey, Elizabeth A., Licht, Christoph, Seto, Winnie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071675/
https://www.ncbi.nlm.nih.gov/pubmed/33912750
http://dx.doi.org/10.1016/j.ekir.2021.01.037
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author Chung, Erin
Tjon, James A.
Nemec, Rosaleen M.
Nalli, Nadya
Harvey, Elizabeth A.
Licht, Christoph
Seto, Winnie
author_facet Chung, Erin
Tjon, James A.
Nemec, Rosaleen M.
Nalli, Nadya
Harvey, Elizabeth A.
Licht, Christoph
Seto, Winnie
author_sort Chung, Erin
collection PubMed
description INTRODUCTION: Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. METHODS: Eligible patients received IV vancomycin 10 mg/kg per dose postdialysis followed by a series of serum vancomycin concentrations collected before, immediately after, 1 hour after, and 4 hours after dialysis. The pharmacokinetic parameters were estimated using 1- and 2-compartment models and a nonlinear least-squares algorithm. RESULTS: Among 42 vancomycin courses in 16 patients, 1 compartment model had the best fit for observed data. The net drug removal was 43 ± 13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h(−1) (standard deviation [SD], 0.11 h(−1)) during the intradialytic period compared with 0.0049 h(−1) (SD, 0.004 h(−1)) when off dialysis. The mean volume of distribution was 0.65 (SD, 0.19) L/kg. Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter for HDF compared with HD (2.1 vs. 3.5 hours). CONCLUSIONS: Based on the simulations, an initial vancomycin dose of 10 mg/kg per dose and redosing postdialysis was optimal to achieve a vancomycin concentration range of 5 to 12 mg/L at 4 hours postdialysis and 24-hour area under the curve over minimum inhibitory concentration of ≥400 hours. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF.
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spelling pubmed-80716752021-04-27 Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration Chung, Erin Tjon, James A. Nemec, Rosaleen M. Nalli, Nadya Harvey, Elizabeth A. Licht, Christoph Seto, Winnie Kidney Int Rep Clinical Research INTRODUCTION: Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. METHODS: Eligible patients received IV vancomycin 10 mg/kg per dose postdialysis followed by a series of serum vancomycin concentrations collected before, immediately after, 1 hour after, and 4 hours after dialysis. The pharmacokinetic parameters were estimated using 1- and 2-compartment models and a nonlinear least-squares algorithm. RESULTS: Among 42 vancomycin courses in 16 patients, 1 compartment model had the best fit for observed data. The net drug removal was 43 ± 13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h(−1) (standard deviation [SD], 0.11 h(−1)) during the intradialytic period compared with 0.0049 h(−1) (SD, 0.004 h(−1)) when off dialysis. The mean volume of distribution was 0.65 (SD, 0.19) L/kg. Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter for HDF compared with HD (2.1 vs. 3.5 hours). CONCLUSIONS: Based on the simulations, an initial vancomycin dose of 10 mg/kg per dose and redosing postdialysis was optimal to achieve a vancomycin concentration range of 5 to 12 mg/L at 4 hours postdialysis and 24-hour area under the curve over minimum inhibitory concentration of ≥400 hours. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF. Elsevier 2021-02-06 /pmc/articles/PMC8071675/ /pubmed/33912750 http://dx.doi.org/10.1016/j.ekir.2021.01.037 Text en © 2021 International Society of Nephrology. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Research
Chung, Erin
Tjon, James A.
Nemec, Rosaleen M.
Nalli, Nadya
Harvey, Elizabeth A.
Licht, Christoph
Seto, Winnie
Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title_full Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title_fullStr Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title_full_unstemmed Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title_short Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration
title_sort pharmacokinetics of vancomycin in pediatric patients receiving intermittent hemodialysis or hemodiafiltration
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071675/
https://www.ncbi.nlm.nih.gov/pubmed/33912750
http://dx.doi.org/10.1016/j.ekir.2021.01.037
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