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Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients

Cefazolin is an antibiotic frequently used for perioperative prophylaxis. Data from healthy adults and pediatric surgery patients were pooled to refine a previously developed population pharmacokinetic (PK) model and to determine the optimal body weight cutoff for selecting fixed doses of either 1 o...

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Autores principales: Schmitz, Michael L., Rubino, Christopher M., Onufrak, Nikolas J., Martinez, Diana Valencia, Licursi, Diane, Karpf, Angela, Cetnarowski, Wes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049034/
https://www.ncbi.nlm.nih.gov/pubmed/33202066
http://dx.doi.org/10.1002/jcph.1785
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author Schmitz, Michael L.
Rubino, Christopher M.
Onufrak, Nikolas J.
Martinez, Diana Valencia
Licursi, Diane
Karpf, Angela
Cetnarowski, Wes
author_facet Schmitz, Michael L.
Rubino, Christopher M.
Onufrak, Nikolas J.
Martinez, Diana Valencia
Licursi, Diane
Karpf, Angela
Cetnarowski, Wes
author_sort Schmitz, Michael L.
collection PubMed
description Cefazolin is an antibiotic frequently used for perioperative prophylaxis. Data from healthy adults and pediatric surgery patients were pooled to refine a previously developed population pharmacokinetic (PK) model and to determine the optimal body weight cutoff for selecting fixed doses of either 1 or 2 g cefazolin to produce exposures in pediatric surgery patients similar to a single 2‐g dose in adults. Regardless of dose used, cefazolin was well tolerated in pediatric patients. A total of 1102 plasma samples from 62 patients from 3 studies were available to assess the previous model. The pooled data set allowed for simplification of the model such that allometrically scaled clearance and volume parameters were found to provide a robust fit while removing unnecessary covariate relationships. Monte Carlo simulations using the final cefazolin population PK model suggested an optimal weight cutoff of 50 kg, in contrast to the previously suggested 60 kg for a single 2‐g dose. Patients at or above this 50‐kg cutoff would receive a 2‐g dose of cefazolin, and those below 50 kg but ≥25 kg would receive a 1‐g dose of cefazolin.
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spelling pubmed-80490342021-04-20 Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients Schmitz, Michael L. Rubino, Christopher M. Onufrak, Nikolas J. Martinez, Diana Valencia Licursi, Diane Karpf, Angela Cetnarowski, Wes J Clin Pharmacol Pediatric Pharmacology Cefazolin is an antibiotic frequently used for perioperative prophylaxis. Data from healthy adults and pediatric surgery patients were pooled to refine a previously developed population pharmacokinetic (PK) model and to determine the optimal body weight cutoff for selecting fixed doses of either 1 or 2 g cefazolin to produce exposures in pediatric surgery patients similar to a single 2‐g dose in adults. Regardless of dose used, cefazolin was well tolerated in pediatric patients. A total of 1102 plasma samples from 62 patients from 3 studies were available to assess the previous model. The pooled data set allowed for simplification of the model such that allometrically scaled clearance and volume parameters were found to provide a robust fit while removing unnecessary covariate relationships. Monte Carlo simulations using the final cefazolin population PK model suggested an optimal weight cutoff of 50 kg, in contrast to the previously suggested 60 kg for a single 2‐g dose. Patients at or above this 50‐kg cutoff would receive a 2‐g dose of cefazolin, and those below 50 kg but ≥25 kg would receive a 1‐g dose of cefazolin. John Wiley and Sons Inc. 2020-12-09 2021-05 /pmc/articles/PMC8049034/ /pubmed/33202066 http://dx.doi.org/10.1002/jcph.1785 Text en © 2020 B. Braun Medical Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Pediatric Pharmacology
Schmitz, Michael L.
Rubino, Christopher M.
Onufrak, Nikolas J.
Martinez, Diana Valencia
Licursi, Diane
Karpf, Angela
Cetnarowski, Wes
Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title_full Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title_fullStr Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title_full_unstemmed Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title_short Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients
title_sort pharmacokinetics and optimal dose selection of cefazolin for surgical prophylaxis of pediatric patients
topic Pediatric Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049034/
https://www.ncbi.nlm.nih.gov/pubmed/33202066
http://dx.doi.org/10.1002/jcph.1785
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