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Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease

PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of β-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4...

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Autores principales: Hassanpour, Rezvan, Ziaie, Shadi, Kobarfard, Farzad, Kouchek, Mehran, Miri, Mirmohammad, Ahmadi Koomleh, Azadeh, Shojaei, Seyedpouzhia, Salarian, Sara, Pourheidar, Elham, Nezarat, Fatemeh, Sistanizad, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787627/
https://www.ncbi.nlm.nih.gov/pubmed/33409684
http://dx.doi.org/10.1007/s00228-020-03062-0
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author Hassanpour, Rezvan
Ziaie, Shadi
Kobarfard, Farzad
Kouchek, Mehran
Miri, Mirmohammad
Ahmadi Koomleh, Azadeh
Shojaei, Seyedpouzhia
Salarian, Sara
Pourheidar, Elham
Nezarat, Fatemeh
Sistanizad, Mohammad
author_facet Hassanpour, Rezvan
Ziaie, Shadi
Kobarfard, Farzad
Kouchek, Mehran
Miri, Mirmohammad
Ahmadi Koomleh, Azadeh
Shojaei, Seyedpouzhia
Salarian, Sara
Pourheidar, Elham
Nezarat, Fatemeh
Sistanizad, Mohammad
author_sort Hassanpour, Rezvan
collection PubMed
description PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of β-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population. METHODS: In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study. RESULTS: On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06–103.18 L), terminal half-life (T1/2) (4.51; 2.67–8.88 h) and decreased clearance (6.52; 4.43–10.16 L/h) have been shown. CONCLUSION: In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target. RETROSPECTIVELY REGISTERED: The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-020-03062-0.
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spelling pubmed-77876272021-01-07 Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease Hassanpour, Rezvan Ziaie, Shadi Kobarfard, Farzad Kouchek, Mehran Miri, Mirmohammad Ahmadi Koomleh, Azadeh Shojaei, Seyedpouzhia Salarian, Sara Pourheidar, Elham Nezarat, Fatemeh Sistanizad, Mohammad Eur J Clin Pharmacol Clinical Trial PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of β-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population. METHODS: In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study. RESULTS: On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06–103.18 L), terminal half-life (T1/2) (4.51; 2.67–8.88 h) and decreased clearance (6.52; 4.43–10.16 L/h) have been shown. CONCLUSION: In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target. RETROSPECTIVELY REGISTERED: The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-020-03062-0. Springer Berlin Heidelberg 2021-01-06 2021 /pmc/articles/PMC7787627/ /pubmed/33409684 http://dx.doi.org/10.1007/s00228-020-03062-0 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Clinical Trial
Hassanpour, Rezvan
Ziaie, Shadi
Kobarfard, Farzad
Kouchek, Mehran
Miri, Mirmohammad
Ahmadi Koomleh, Azadeh
Shojaei, Seyedpouzhia
Salarian, Sara
Pourheidar, Elham
Nezarat, Fatemeh
Sistanizad, Mohammad
Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title_full Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title_fullStr Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title_full_unstemmed Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title_short Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
title_sort evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787627/
https://www.ncbi.nlm.nih.gov/pubmed/33409684
http://dx.doi.org/10.1007/s00228-020-03062-0
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