Population Pharmacokinetics and Pharmacodynamics of Enoxaparin in Unstable Angina and Non-ST-segment Elevation Myocardial Infarction

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2003 Sep 13

PMID 12968985

Citations 14

Authors

Rene Bruno

Pascale Baille

Sylvie Retout

Nicole Vivier

Christine Veyrat-Follet

Ger-Jan Sanderink

Richard Becker

Elliott M Antman

Affiliations

Soon will be listed here.

Abstract

Aims: A major concern with any antithrombotic therapy is an increase in the risk of haemorrhage. The aim of this study was to analyse population pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) relationships for enoxaparin in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI), which may help predict risk of haemorrhage.

Methods: Anti-factor Xa (anti-Xa) activity was measured as marker of enoxaparin concentration in 448 patients receiving the drug as a single 30-mg intravenous bolus followed by 1.0 or 1.25 mg kg(-1) subcutaneously twice a day. A population pharmacokinetic analysis was conducted and individual estimates of enoxaparin clearance and area under the curve were tested as prognostic factors for the occurrence of haemorrhagic episodes.

Results: Basic population PK parameters were an enoxaparin clearance of 0.733 l h(-1)[95% confidence interval (CI) 0.698, 0.738], a distribution volume of 5.24 l (95% CI 4.20, 6.28) and an elimination half-life of 5.0 h. Enoxaparin clearance was significantly related to patient weight and creatinine clearance, and was the only independent predictor of experiencing both all (10.7%, P = 0.0013) and major (2.2%, P = 0.0004) haemorrhagic events. A creatinine clearance of 30 ml min(-1) was associated with a decrease in enoxaparin clearance of 27% compared with that in a patient with a median creatinine clearance of 88 ml min-1, and was related to a 1.5- and 3.8-fold increase in the risk of 'all' and 'major' haemorrhagic episodes, respectively.

Conclusions: Enoxaparin clearance depends on body weight, and, therefore, weight-adjusted dosing is recommended to minimize interpatient variability in drug exposure and the risk of haemorrhage. The importance of an increased risk of haemorrhage with decreasing renal function must be weighed against the benefit of treatment with enoxaparin in patients with UA and NSTEMI.

Citing Articles

A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin.

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Sustained drug-related reaction with eosinophilia and systemic symptoms (DRESS) triggered by low molecular weight heparins in COVID-19: management and precision diagnosis.

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Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention.

Sumaya W, Parker W, Judge H, Hall I, Orme R, Adam Z Platelets. 2020; 32(4):555-559.

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Dosing of Enoxaparin in Renal Impairment.

Shaikh S, Regal R P T. 2017; 42(4):245-249.

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Sacha G, Greenlee K, Ketz J J Thromb Thrombolysis. 2016; 42(4):479-85.

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