Pharmacokinetics of enoxaparin in COVID-19 critically ill patients
Copyright © 2021 Elsevier Ltd. All rights reserved..
BACKGROUND: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing.
OBJECTIVES: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients.
METHODS: This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration.
RESULTS: A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment.
CONCLUSION: In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:205 |
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| Enthalten in: |
Thrombosis research - 205(2021) vom: 15. Sept., Seite 120-127 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zufferey, Paul Jacques [VerfasserIn] |
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| Links: |
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| Themen: |
Adult |
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| Anmerkungen: |
Date Completed 12.08.2021 Date Revised 17.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.thromres.2021.07.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328559377 |
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| 100 | 1 | |a Zufferey, Paul Jacques |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics of enoxaparin in COVID-19 critically ill patients |
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| 500 | |a Date Completed 12.08.2021 | ||
| 500 | |a Date Revised 17.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing | ||
| 520 | |a OBJECTIVES: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients | ||
| 520 | |a METHODS: This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration | ||
| 520 | |a RESULTS: A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment | ||
| 520 | |a CONCLUSION: In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adult | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Critical care | |
| 650 | 4 | |a Embolism and thrombosis | |
| 650 | 4 | |a Enoxaparin | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Enoxaparin |2 NLM | |
| 700 | 1 | |a Dupont, Annabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Lanoiselée, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Bauters, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Poissy, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Goutay, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Jean, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Caplan, Morgan |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Lionel |e verfasserin |4 aut | |
| 700 | 1 | |a Susen, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Delavenne, Xavier |e verfasserin |4 aut | |
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