Pharmacokinetics of enoxaparin in COVID-19 critically ill patients. Issue 205 (September 2021)

• Record Type: Journal Article
• Authors: Zufferey, Paul Jacques; Dupont, Annabelle; Lanoiselée, Julien; Bauters, Anne; Poissy, Julien; Goutay, Julien; Jean, Laurent; Caplan, Morgan; Levy, Lionel; Susen, Sophie; Delavenne, Xavier
• Is Part Of: Thrombosis research. Issue 205(2021)
• Page Start: 120
• Page End: 127
• Publication Date: 2021-09
• Subjects: Enoxaparin -- COVID-19 -- Pharmacokinetics -- Critical care -- Embolism and thrombosis -- Adult; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2021.07.010
• Languages: English
• ISSNs: 0049-3848

Abstract

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. Highlights: Critical care COVID-19 patients are at high risk of venous thrombosis. Population pharmacokinetics of enoxaparin in ICU COVID-19 patients were modeled. Clearance and volume of distribution were high resulting in low anti-Xa exposure. Enoxaparin 40 mg qd was suboptimal in ICU to attain thromboprophylactic target levels.