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.
Subject(s)
COVID-19 , Enoxaparin , Anticoagulants , Critical Illness , Enoxaparin/therapeutic use , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
ABSTRACT: In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug-drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.
Subject(s)
Acute Kidney Injury/metabolism , COVID-19/metabolism , Drug Monitoring/methods , Pyrazoles/metabolism , Pyridones/metabolism , Renal Elimination/drug effects , Teaching Rounds/methods , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Aged, 80 and over , Antiviral Agents/adverse effects , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Drug Interactions/physiology , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/metabolism , Factor Xa Inhibitors/therapeutic use , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/prevention & control , Male , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyridones/adverse effects , Pyridones/therapeutic use , Renal Elimination/physiology , Severity of Illness Index , Time Factors , COVID-19 Drug TreatmentABSTRACT
Hydroxychloroquine (HCQ) appears to be a promising treatment for COVID-19. However, all ongoing clinical trials with HCQ use different dosing regimens, resulting in various concentrations. Pharmacokinetic studies are therefore needed to define the optimal dosing regimen.