Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 89, Issue 5, Pages 1617-1628Publisher
WILEY
DOI: 10.1111/bcp.15634
Keywords
critical care; haematology; infectious diseases; intensive care; pharmacodynamics; pharmacokinetics; modelling and simulation; thrombosis
Categories
Ask authors/readers for more resources
In this study, a population pharmacokinetic analysis showed that the optimal dosing regimen of nadroparin for COVID-19 ICU patients is 5700 IU BID, which can achieve the target anti-Xa levels. The clearance of nadroparin is related to inflammation parameters, corticosteroids, vasopressors, and renal clearance in critically ill patients.
AimsNadroparin is administered to COVID-19 intensive care unit (ICU) patients as thromboprophylaxis. Despite existing population pharmacokinetic (PK) models for nadroparin in literature, the population PK of nadroparin in COVID-19 ICU patients is unknown. Moreover, optimal dosing regimens achieving anti-Xa target levels (0.3-0.7 IU/mL) are unknown. Therefore, a population PK analysis was conducted to investigate different dosing regimens of nadroparin in COVID-19 ICU patients. MethodsAnti-Xa levels (n = 280) from COVID-19 ICU patients (n = 65) receiving twice daily (BID) 5700 IU of subcutaneous nadroparin were collected to perform a population PK analysis with NONMEM v7.4.1. Using Monte Carlo simulations (n = 1000), predefined dosing regimens were evaluated. ResultsA 1-compartment model with an absorption compartment adequately described the measured anti-Xa levels with interindividual variability estimated for clearance (CL). Inflammation parameters C-reactive protein, D-dimer and estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equation allowed to explain the interindividual variability of CL. Moreover, CL was decreased in patients receiving corticosteroids (22.5%) and vasopressors (25.1%). Monte Carlo simulations demonstrated that 5700 IU BID was the most optimal dosing regimen of the simulated regimens for achieving prespecified steady-state t = 4 h anti-Xa levels with 56.7% on target (0.3-0.7 IU/mL). ConclusionIn our study, clearance of nadroparin is associated with an increase in inflammation parameters, use of corticosteroids, vasopression and renal clearance in critically ill patients. Furthermore, of the simulated regimens, targeted anti-Xa levels were most adequately achieved with a dosing regimen of 5700 IU BID. Future studies are needed to elucidate the underlying mechanisms of found covariate relationships.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available