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Pharmacokinetics of enoxaparin in COVID-19 critically ill patients.
Zufferey, Paul Jacques; Dupont, Annabelle; Lanoiselée, Julien; Bauters, Anne; Poissy, Julien; Goutay, Julien; Jean, Laurent; Caplan, Morgan; Levy, Lionel; Susen, Sophie; Delavenne, Xavier.
  • Zufferey PJ; INSERM, U1059, Vascular Dysfunction and Hemostasis, F-42023 Saint-Etienne, France; Department of Anesthesia and Critical Care, University Hospital of Saint-Etienne, F-42055 Saint-Etienne, France; Clinical Pharmacology Department, University Hospital of Saint-Etienne, F-42055 Saint Etienne, France. E
  • Dupont A; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 EGID, F-59000 Lille, France.
  • Lanoiselée J; INSERM, U1059, Vascular Dysfunction and Hemostasis, F-42023 Saint-Etienne, France; Department of Anesthesia and Critical Care, University Hospital of Saint-Etienne, F-42055 Saint-Etienne, France.
  • Bauters A; CHU Lille, Institut d'Hématologie-Transfusion, F-59000 Lille, France.
  • Poissy J; Univ. Lille, Inserm U1285, CHU Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.
  • Goutay J; CHU Lille, Intensive Care Department, Pôle de Réanimation, F-59000 Lille, France.
  • Jean L; Department of Anesthesia and Critical Care, University Hospital of Saint-Etienne, F-42055 Saint-Etienne, France.
  • Caplan M; CHU Lille, Intensive Care Department, Pôle de Réanimation, F-59000 Lille, France.
  • Levy L; Department of Anesthesia and Critical Care, University Hospital of Saint-Etienne, F-42055 Saint-Etienne, France.
  • Susen S; Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 EGID, F-59000 Lille, France.
  • Delavenne X; INSERM, U1059, Vascular Dysfunction and Hemostasis, F-42023 Saint-Etienne, France; Clinical Pharmacology Department, University Hospital of Saint-Etienne, F-42055 Saint Etienne, France; University of Lyon, Saint-Etienne F-42023, France.
Thromb Res ; 205: 120-127, 2021 09.
Статья в английский | MEDLINE | ID: covidwho-1324320
ABSTRACT

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.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Enoxaparin / COVID-19 Тип исследования: Наблюдательное исследование / Прогностическое исследование Пределы темы: Люди Язык: английский Журнал: Thromb Res Год: 2021 Тип: Статья

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Enoxaparin / COVID-19 Тип исследования: Наблюдательное исследование / Прогностическое исследование Пределы темы: Люди Язык: английский Журнал: Thromb Res Год: 2021 Тип: Статья