A randomised assessment of the pharmacokinetic, pharmacodynamic and safety interaction between apixaban and enoxaparin in healthy subjects

Yu Chen Barrett; Jessie Wang; Yan Song; Janice Pursley; Philip Wastall; Robert Wright; Frank LaCreta; Charles Frost

doi:10.1160/TH11-09-0634

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2012; 107(05): 916-924
DOI: 10.1160/TH11-09-0634

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

A randomised assessment of the pharmacokinetic, pharmacodynamic and safety interaction between apixaban and enoxaparin in healthy subjects

Yu Chen Barrett

¹Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Plainsboro, New Jersey, USA

,

Jessie Wang

²Exploratory Development Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey, USA

,

Yan Song

¹Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Plainsboro, New Jersey, USA

,

Janice Pursley

³Analytical and Bioanalytical Department, Bristol-Myers Squibb, Princeton, New Jersey, USA

,

Philip Wastall

¹Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Plainsboro, New Jersey, USA

,

Robert Wright

⁴Global Medical Affairs, Bristol-Myers Squibb, Princeton, New Jersey, USA

,

Frank LaCreta

¹Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Plainsboro, New Jersey, USA

,

Charles Frost

¹Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Plainsboro, New Jersey, USA

› Institutsangaben

Abstract

Summary

Following major orthopaedic surgery, guidelines usually recommend continued thromboprophylaxis after hospitalisation. The availability of an effective oral anticoagulant with an acceptable safety profile that does not require routine clinical monitoring may lead clinicians to switch patients from subcutaneous to an oral therapy either during hospitalisation or at discharge. The purpose of this study was to assess the effect of enoxaparin on the pharmacokinetics, pharmacodynamics and safety of apixaban, an oral, direct inhibitor of coagulation factor Xa. In this four-period, crossover study, 20 healthy subjects were randomised to receive single doses of apixaban 5 mg orally; enoxaparin 40 mg subcutaneously; apixaban 5 mg and enoxaparin 40 mg concomitantly; and apixaban 5 mg followed 6 hours (h) after by enoxaparin 40 mg. Pharmacokinetics of apixaban were not affected by enoxaparin. Average peak pharmacodynamic effect, measured by anti-Xa activity, was 1.36 U/ml after administration of apixaban and was 0.42 U/ml after enoxaparin. Following co-administration of apixaban and enoxaparin, peak anti-Xa activity was 42% higher than for apixaban alone. Following administration of enoxaparin 6 h after apixaban, peak anti-Xa activity was 15% higher than for apixaban alone. In conclusion, enoxaparin had no effect on the pharmacokinetics of apixaban. The increase in anti-Xa activity after co-administration was modest and appeared to be additive. Peak anti-Xa activity increases are mitigated by separating administration of subcutaneous anticoagulation and apixaban when switching between therapies; the potential for pharmacodynamic interaction may be further mitigated by transitioning at the next scheduled dose (12 h).

Keywords

Apixaban - factor Xa inhibitor - drug switching - pharmacokinetics/pharmacodynamics - thromboprophylaxis

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