Cargando…

The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body

Several studies have addressed the poor stability of meropenem in aqueous solutions, though not considering the main degradation product, the open-ring metabolite (ORM) form. In the present work, we elucidate the metabolic fate of meropenem and ORM from continuous infusion to the human bloodstream....

Descripción completa

Detalles Bibliográficos
Autores principales: Liebchen, Uwe, Rakete, Sophie, Vogeser, Michael, Arend, Florian M., Kinast, Christina, Scharf, Christina, Zoller, Michael, Schönermarck, Ulf, Paal, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231794/
https://www.ncbi.nlm.nih.gov/pubmed/34198482
http://dx.doi.org/10.3390/antibiotics10060715
_version_ 1783713495790911488
author Liebchen, Uwe
Rakete, Sophie
Vogeser, Michael
Arend, Florian M.
Kinast, Christina
Scharf, Christina
Zoller, Michael
Schönermarck, Ulf
Paal, Michael
author_facet Liebchen, Uwe
Rakete, Sophie
Vogeser, Michael
Arend, Florian M.
Kinast, Christina
Scharf, Christina
Zoller, Michael
Schönermarck, Ulf
Paal, Michael
author_sort Liebchen, Uwe
collection PubMed
description Several studies have addressed the poor stability of meropenem in aqueous solutions, though not considering the main degradation product, the open-ring metabolite (ORM) form. In the present work, we elucidate the metabolic fate of meropenem and ORM from continuous infusion to the human bloodstream. We performed in vitro infusate stability tests at ambient temperature with 2% meropenem reconstituted in 0.9% normal saline, and body temperature warmed buffered human serum with 2, 10, and 50 mg/L meropenem, covering the therapeutic range. We also examined meropenem and ORM levels over several days in six critically ill patients receiving continuous infusions. Meropenem exhibited a constant degradation rate of 0.006/h and 0.025/h in normal saline at 22 °C and serum at 37 °C, respectively. Given that 2% meropenem remains stable for 17.5 h in normal saline (≥90% of the initial concentration), we recommend replacement of the infusate every 12 h. Our patients showed inter-individually highly variable, but intra-individually constant molar ORM/(meropenem + ORM) ratios of 0.21–0.52. Applying a population pharmacokinetic approach using the degradation rate in serum, spontaneous degradation accounted for only 6% of the total clearance.
format Online
Article
Text
id pubmed-8231794
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-82317942021-06-26 The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body Liebchen, Uwe Rakete, Sophie Vogeser, Michael Arend, Florian M. Kinast, Christina Scharf, Christina Zoller, Michael Schönermarck, Ulf Paal, Michael Antibiotics (Basel) Article Several studies have addressed the poor stability of meropenem in aqueous solutions, though not considering the main degradation product, the open-ring metabolite (ORM) form. In the present work, we elucidate the metabolic fate of meropenem and ORM from continuous infusion to the human bloodstream. We performed in vitro infusate stability tests at ambient temperature with 2% meropenem reconstituted in 0.9% normal saline, and body temperature warmed buffered human serum with 2, 10, and 50 mg/L meropenem, covering the therapeutic range. We also examined meropenem and ORM levels over several days in six critically ill patients receiving continuous infusions. Meropenem exhibited a constant degradation rate of 0.006/h and 0.025/h in normal saline at 22 °C and serum at 37 °C, respectively. Given that 2% meropenem remains stable for 17.5 h in normal saline (≥90% of the initial concentration), we recommend replacement of the infusate every 12 h. Our patients showed inter-individually highly variable, but intra-individually constant molar ORM/(meropenem + ORM) ratios of 0.21–0.52. Applying a population pharmacokinetic approach using the degradation rate in serum, spontaneous degradation accounted for only 6% of the total clearance. MDPI 2021-06-14 /pmc/articles/PMC8231794/ /pubmed/34198482 http://dx.doi.org/10.3390/antibiotics10060715 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liebchen, Uwe
Rakete, Sophie
Vogeser, Michael
Arend, Florian M.
Kinast, Christina
Scharf, Christina
Zoller, Michael
Schönermarck, Ulf
Paal, Michael
The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title_full The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title_fullStr The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title_full_unstemmed The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title_short The Role of Non-Enzymatic Degradation of Meropenem—Insights from the Bottle to the Body
title_sort role of non-enzymatic degradation of meropenem—insights from the bottle to the body
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231794/
https://www.ncbi.nlm.nih.gov/pubmed/34198482
http://dx.doi.org/10.3390/antibiotics10060715
work_keys_str_mv AT liebchenuwe theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT raketesophie theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT vogesermichael theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT arendflorianm theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT kinastchristina theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT scharfchristina theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT zollermichael theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT schonermarckulf theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT paalmichael theroleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT liebchenuwe roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT raketesophie roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT vogesermichael roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT arendflorianm roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT kinastchristina roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT scharfchristina roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT zollermichael roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT schonermarckulf roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody
AT paalmichael roleofnonenzymaticdegradationofmeropeneminsightsfromthebottletothebody