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1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study

BACKGROUND: There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients. METHODS: We prospectively enrolled...

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Autores principales: Jung, Younghee, Lee, Dong-Hwan, Soo Kim, Hyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808961/
http://dx.doi.org/10.1093/ofid/ofz360.1404
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author Jung, Younghee
Lee, Dong-Hwan
Soo Kim, Hyoung
author_facet Jung, Younghee
Lee, Dong-Hwan
Soo Kim, Hyoung
author_sort Jung, Younghee
collection PubMed
description BACKGROUND: There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients. METHODS: We prospectively enrolled adult patients who were undergoing ECMO and receiving vancomycin from July 2018 to April 2019. After initial dose of vancomycin was administrated, serial blood samples (seven to nine times per patient) were drawn before the next dose. A population PK model for vancomycin was developed using a nonlinear mixed-effect modeling. Age, sex, creatinine clearance, and body weight were tested as potential covariates in the model. Model selection was based on log-likelihood test, model diagnostic plots, and clinical plausibility. RESULTS: Fourteen patients were included over the period. Ten received venovenous, three venoarterial, and one both type ECMO. Eleven were men and the median age was 54 (interquartile range 45–66.3). Mean estimated glomerular filtration rate (eGFR) was 69 ± 46 mL/minute/1.73m(2) by the modification of diet in renal disease equation. A total of 123 vancomycin concentrations from the patients were included in the analysis. The population PK of vancomycin was best described by a two-compartment model with a proportional residual error model. The typical value (%between-subject variability) for total clearance was estimated to be 4.33 L/h (21.6%), central volume of distribution was 9.22 L, the intercompartmental clearance was 10.75 L/hr (34.9%) and the peripheral volume of distribution was 19.6 L (26.6%). The proportional residual variability was 8.81%. Creatinine clearance significantly influenced vancomycin clearance (CL). The proposed equation to estimate vancomycin clearance in Korean ECMO patients was CL = 4.33 + 0.199 × (eGFR – 56). CONCLUSION: A two-compartment population PK model successfully describes vancomycin PK profiles in Korean ECMO patients. The model could be used to optimize the dosing regimen if more data become available from currently ongoing clinical study. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68089612019-10-28 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study Jung, Younghee Lee, Dong-Hwan Soo Kim, Hyoung Open Forum Infect Dis Abstracts BACKGROUND: There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients. METHODS: We prospectively enrolled adult patients who were undergoing ECMO and receiving vancomycin from July 2018 to April 2019. After initial dose of vancomycin was administrated, serial blood samples (seven to nine times per patient) were drawn before the next dose. A population PK model for vancomycin was developed using a nonlinear mixed-effect modeling. Age, sex, creatinine clearance, and body weight were tested as potential covariates in the model. Model selection was based on log-likelihood test, model diagnostic plots, and clinical plausibility. RESULTS: Fourteen patients were included over the period. Ten received venovenous, three venoarterial, and one both type ECMO. Eleven were men and the median age was 54 (interquartile range 45–66.3). Mean estimated glomerular filtration rate (eGFR) was 69 ± 46 mL/minute/1.73m(2) by the modification of diet in renal disease equation. A total of 123 vancomycin concentrations from the patients were included in the analysis. The population PK of vancomycin was best described by a two-compartment model with a proportional residual error model. The typical value (%between-subject variability) for total clearance was estimated to be 4.33 L/h (21.6%), central volume of distribution was 9.22 L, the intercompartmental clearance was 10.75 L/hr (34.9%) and the peripheral volume of distribution was 19.6 L (26.6%). The proportional residual variability was 8.81%. Creatinine clearance significantly influenced vancomycin clearance (CL). The proposed equation to estimate vancomycin clearance in Korean ECMO patients was CL = 4.33 + 0.199 × (eGFR – 56). CONCLUSION: A two-compartment population PK model successfully describes vancomycin PK profiles in Korean ECMO patients. The model could be used to optimize the dosing regimen if more data become available from currently ongoing clinical study. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6808961/ http://dx.doi.org/10.1093/ofid/ofz360.1404 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Jung, Younghee
Lee, Dong-Hwan
Soo Kim, Hyoung
1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title_full 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title_fullStr 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title_full_unstemmed 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title_short 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
title_sort 1540. a population pharmacokinetic model for vancomycin in korean patients receiving extracorporeal membrane oxygenation therapy: a prospective study
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808961/
http://dx.doi.org/10.1093/ofid/ofz360.1404
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