Skip to main content
Top
Published in: Clinical Pharmacokinetics 12/2003

01-10-2003 | Review Article

Pharmacodynamic and Pharmacokinetic Properties of Enoxaparin

Implications for Clinical Practice

Authors: Dr Jawed Fareed, Debra Hoppensteadt, Jeanine Walenga, Omer Iqbal, Qing Ma, Walter Jeske, Taqdees Sheikh

Published in: Clinical Pharmacokinetics | Issue 12/2003

Login to get access

Abstract

Enoxaparin is a low-molecular-weight heparin (LMWH) that differs substantially from unfractionated heparin (UFH) in its pharmacodynamic and pharmacokinetic properties. Some of the pharmacodynamic features of enoxaparin that distinguish it from UFH are a higher ratio of anti-Xa to anti-IIa activity, more consistent release of tissue factor pathway inhibitor, weaker interactions with platelets and less inhibition of bone formation. Enoxaparin has a higher and more consistent bioavailability after subcutaneous administration than UFH, a longer plasma half-life and is less strongly bound to plasma proteins. These properties mean that enoxaparin provides a more reliable anticoagulant effect without the need for laboratory monitoring, and also offers the convenience of once-daily administration. Clinical studies have confirmed that these pharmacological advantages translate into improved outcomes. There are important pharmacokinetic and pharmacodynamic differences between enoxaparin, other LMWHs and UFH, and therefore these molecules cannot be regarded as interchangeable.
Literature
1.
go back to reference Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 (5 Suppl.): 489S–510SPubMedCrossRef Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 (5 Suppl.): 489S–510SPubMedCrossRef
2.
go back to reference Frydman A. Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis 1996; 26 Suppl. 2: 24–38PubMed Frydman A. Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis 1996; 26 Suppl. 2: 24–38PubMed
3.
go back to reference Kandrotas RJ. Heparin pharmacokinetics and pharmacodynamics. Clin Pharmacokinetics 1992; 22(5): 359–74CrossRef Kandrotas RJ. Heparin pharmacokinetics and pharmacodynamics. Clin Pharmacokinetics 1992; 22(5): 359–74CrossRef
4.
go back to reference Weitz JI, Hudoba M, Massel D, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385–91PubMedCrossRef Weitz JI, Hudoba M, Massel D, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385–91PubMedCrossRef
5.
6.
go back to reference Ginsberg JS, Kowalchuk G, Hirsh J, et al. Heparin effect on bone density. Thromb Haemost 1990; 64: 286–9PubMed Ginsberg JS, Kowalchuk G, Hirsh J, et al. Heparin effect on bone density. Thromb Haemost 1990; 64: 286–9PubMed
7.
go back to reference Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1–17PubMed Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1–17PubMed
8.
go back to reference Fareed J, Jeske W, Hoppensteadt D, et al. Are all available low-molecular-weight heparin preparations the same? Semin Thromb Hemost 1996; 22Suppl. 1: 77–91PubMed Fareed J, Jeske W, Hoppensteadt D, et al. Are all available low-molecular-weight heparin preparations the same? Semin Thromb Hemost 1996; 22Suppl. 1: 77–91PubMed
9.
go back to reference Brieger D, Dawes J. Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins. Thromb Haemost 1997; 77: 317–22PubMed Brieger D, Dawes J. Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins. Thromb Haemost 1997; 77: 317–22PubMed
10.
go back to reference Cohen M, Demeers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease: efficacy and safety of subcutaneous enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337: 447–52PubMedCrossRef Cohen M, Demeers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease: efficacy and safety of subcutaneous enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337: 447–52PubMedCrossRef
11.
go back to reference Fareed J, Walenga JM, Hoppensteadt D, et al. Comparative study on the in vitro and in vivo activities of seven low-molecular-weight heparins. Haemostasis 1988; 18 Suppl. 3: 3–15PubMed Fareed J, Walenga JM, Hoppensteadt D, et al. Comparative study on the in vitro and in vivo activities of seven low-molecular-weight heparins. Haemostasis 1988; 18 Suppl. 3: 3–15PubMed
12.
go back to reference Padilla A, Gray E, Pepper DS, et al. Inhibition of thrombin generation by heparin and low molecular weight (LMW) heparins in the absence and presence of platelet factor 4 (PF4). Br J Haematol 1992; 82: 406–13PubMedCrossRef Padilla A, Gray E, Pepper DS, et al. Inhibition of thrombin generation by heparin and low molecular weight (LMW) heparins in the absence and presence of platelet factor 4 (PF4). Br J Haematol 1992; 82: 406–13PubMedCrossRef
13.
go back to reference Fareed J, Walenga JM, Hoppensteadt D, et al. Biochemical and pharmacologic inequivalence of low molecular weight heparins. Ann N Y Acad Sci 1989; 556: 333–53PubMedCrossRef Fareed J, Walenga JM, Hoppensteadt D, et al. Biochemical and pharmacologic inequivalence of low molecular weight heparins. Ann N Y Acad Sci 1989; 556: 333–53PubMedCrossRef
14.
go back to reference Béguin S, Lindhout T, Hemker HC. The mode of action of heparin in plasma. Thromb Haemost 1988; 60: 457–62PubMed Béguin S, Lindhout T, Hemker HC. The mode of action of heparin in plasma. Thromb Haemost 1988; 60: 457–62PubMed
15.
go back to reference Bara L, Bloch MF, Zitoun D, et al. Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor. Thromb Res 1993; 69: 443–52PubMedCrossRef Bara L, Bloch MF, Zitoun D, et al. Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor. Thromb Res 1993; 69: 443–52PubMedCrossRef
16.
go back to reference Matthiasson SE, Lindblad B, Stjernquist U, et al. The haemorrhagic effect of low molecular weight heparins, dermatan sulphate and hirudin. Haemostasis 1995; 25: 203–11PubMed Matthiasson SE, Lindblad B, Stjernquist U, et al. The haemorrhagic effect of low molecular weight heparins, dermatan sulphate and hirudin. Haemostasis 1995; 25: 203–11PubMed
17.
go back to reference Bang CJ, Berstad A, Talstad I. Haemorrhagic effects of unfractionated and two low molecular weight heparins, enoxaparin and fragmin, in rats. Haemostasis 1991; 21: 30–6PubMed Bang CJ, Berstad A, Talstad I. Haemorrhagic effects of unfractionated and two low molecular weight heparins, enoxaparin and fragmin, in rats. Haemostasis 1991; 21: 30–6PubMed
18.
go back to reference Bendz B, Hansen J-B, Andersen TO, et al. Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins. Br J Haematol 1999; 107: 756–62PubMedCrossRef Bendz B, Hansen J-B, Andersen TO, et al. Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins. Br J Haematol 1999; 107: 756–62PubMedCrossRef
19.
go back to reference Hansen J-B, Sandset PM, Huseby KR, et al. Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action. Br J Haematol 1998; 101: 638–46PubMedCrossRef Hansen J-B, Sandset PM, Huseby KR, et al. Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action. Br J Haematol 1998; 101: 638–46PubMedCrossRef
20.
go back to reference Bendetowicz AV, Kai H, Knebel R, et al. The effect of subcutaneous injection of unfractionated and low molecular weight heparin on thrombin generation in platelet rich plasma: a study in human volunteers. Thromb Haemost 1994; 72: 705–12PubMed Bendetowicz AV, Kai H, Knebel R, et al. The effect of subcutaneous injection of unfractionated and low molecular weight heparin on thrombin generation in platelet rich plasma: a study in human volunteers. Thromb Haemost 1994; 72: 705–12PubMed
21.
go back to reference Schoen P, Lindhout T, Franssen J, et al. Low molecular weight heparin-catalyzed inactivation of factor Xa and thrombin by antithrombin III: effect of platelet factor 4. Thromb Haemost 1991; 66: 435–41PubMed Schoen P, Lindhout T, Franssen J, et al. Low molecular weight heparin-catalyzed inactivation of factor Xa and thrombin by antithrombin III: effect of platelet factor 4. Thromb Haemost 1991; 66: 435–41PubMed
22.
go back to reference Beguin S, Mardiguian J, Lindhout T, et al. The mode of action of low molecular weight heparin preparation (PK10169) and two of its major components on thrombin generation in plasma. Thromb Haemost 1989; 61: 30–4PubMed Beguin S, Mardiguian J, Lindhout T, et al. The mode of action of low molecular weight heparin preparation (PK10169) and two of its major components on thrombin generation in plasma. Thromb Haemost 1989; 61: 30–4PubMed
23.
go back to reference Messmore Jr HL, Griffin B, Fareed J, et al. In vitro studies of the interaction of heparin, low molecular weight heparin and heparinoids with platelets. Ann N Y Acad Sci 1989; 556: 217–32PubMedCrossRef Messmore Jr HL, Griffin B, Fareed J, et al. In vitro studies of the interaction of heparin, low molecular weight heparin and heparinoids with platelets. Ann N Y Acad Sci 1989; 556: 217–32PubMedCrossRef
24.
go back to reference Cade JF, Buchanan MR, Boneu B, et al. A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation. Thromb Res 1984; 35: 613–25PubMedCrossRef Cade JF, Buchanan MR, Boneu B, et al. A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation. Thromb Res 1984; 35: 613–25PubMedCrossRef
25.
go back to reference Brace LD, Fareed J, Tomeo J, et al. Biochemical and pharmacological studies on the interaction of PK 10160 and its subfractions with human platelets. Haemostasis 1986; 16: 93–105PubMed Brace LD, Fareed J, Tomeo J, et al. Biochemical and pharmacological studies on the interaction of PK 10160 and its subfractions with human platelets. Haemostasis 1986; 16: 93–105PubMed
26.
go back to reference Xiao Z, Theroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 1998; 97: 251–6PubMedCrossRef Xiao Z, Theroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 1998; 97: 251–6PubMedCrossRef
27.
go back to reference Fernandez F, N’guyen P, Van Ryn J, et al. Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect. Thromb Res 1986; 43: 491–5PubMedCrossRef Fernandez F, N’guyen P, Van Ryn J, et al. Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect. Thromb Res 1986; 43: 491–5PubMedCrossRef
28.
go back to reference Mirshahi M, Soria J, Neuhart E, et al. Effect of heparin and enoxaparin on platelet interaction with fibrin clots. Thromb Res 1992; 65: 187–91PubMedCrossRef Mirshahi M, Soria J, Neuhart E, et al. Effect of heparin and enoxaparin on platelet interaction with fibrin clots. Thromb Res 1992; 65: 187–91PubMedCrossRef
29.
go back to reference Van Rijn JLML, Trillou M, Mardiguian T, et al. Selective binding of heparins to human endothelial cells: implications for pharmacokinetics. Thromb Res 1987; 45: 211–22PubMedCrossRef Van Rijn JLML, Trillou M, Mardiguian T, et al. Selective binding of heparins to human endothelial cells: implications for pharmacokinetics. Thromb Res 1987; 45: 211–22PubMedCrossRef
30.
go back to reference Zammit A, Pepper DS, Dawes J. Interaction of immobilised unfractionated and LMW heparins with proteins in whole human plasma. Thromb Haemost 1993; 70: 951–8PubMed Zammit A, Pepper DS, Dawes J. Interaction of immobilised unfractionated and LMW heparins with proteins in whole human plasma. Thromb Haemost 1993; 70: 951–8PubMed
31.
go back to reference Young E, Cosmi B, Weitz J, et al. Comparison of the nonspecific binding of unfractionated heparin and low molecular weight heparin (enoxaparin) to plasma proteins. Thromb Haemost 1993; 70: 625–30PubMed Young E, Cosmi B, Weitz J, et al. Comparison of the nonspecific binding of unfractionated heparin and low molecular weight heparin (enoxaparin) to plasma proteins. Thromb Haemost 1993; 70: 625–30PubMed
32.
go back to reference Young E, Wells P, Holloway S, et al. Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71: 300–4PubMed Young E, Wells P, Holloway S, et al. Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71: 300–4PubMed
33.
go back to reference Bhandari M, Hirsh J, Weitz JI, et al. The effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb Haemost 1998; 80: 413–7PubMed Bhandari M, Hirsh J, Weitz JI, et al. The effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb Haemost 1998; 80: 413–7PubMed
34.
go back to reference Fareed J, Walenga JM, Hoppensteadt DA, et al. Laboratory studies on the intravenous and subcutaneous administration of PK 10169 in man. Haemostasis 1986; 16: 123–38PubMed Fareed J, Walenga JM, Hoppensteadt DA, et al. Laboratory studies on the intravenous and subcutaneous administration of PK 10169 in man. Haemostasis 1986; 16: 123–38PubMed
35.
go back to reference Montalescot G, Philippe F, Ankri A, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial. Circulation 1998; 98: 294–9PubMedCrossRef Montalescot G, Philippe F, Ankri A, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial. Circulation 1998; 98: 294–9PubMedCrossRef
36.
go back to reference Hodl R, Hubert K, Kraxner W, et al. Comparison of effects of dalteparin and enoxaparin on hemostatic parameters and von Willebrand factor in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction. Am J Cardiol 2002; 89(5): 589–92PubMedCrossRef Hodl R, Hubert K, Kraxner W, et al. Comparison of effects of dalteparin and enoxaparin on hemostatic parameters and von Willebrand factor in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction. Am J Cardiol 2002; 89(5): 589–92PubMedCrossRef
37.
go back to reference Montalescot G, Collet JP, Lison L, et al. Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina. J Am Coll Cardiol 2000; 36(1): 110–4PubMedCrossRef Montalescot G, Collet JP, Lison L, et al. Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina. J Am Coll Cardiol 2000; 36(1): 110–4PubMedCrossRef
38.
go back to reference Cornelli U, Fareed J. Human pharmacokinetics of low molecular weight heparins. Semin Thromb Hemost 1999; 25 Suppl. 3: 57–61PubMed Cornelli U, Fareed J. Human pharmacokinetics of low molecular weight heparins. Semin Thromb Hemost 1999; 25 Suppl. 3: 57–61PubMed
39.
go back to reference Dawes J. Comparison of the pharmacokinetics of enoxaparin (Clexane®) and unfractionated heparin. Acta Chir Scand 1990; 156 (556 Suppl.): 68–74 Dawes J. Comparison of the pharmacokinetics of enoxaparin (Clexane®) and unfractionated heparin. Acta Chir Scand 1990; 156 (556 Suppl.): 68–74
40.
go back to reference Azizi M, Veyssier-Belot C, Alhenc-Gelas M, et al. Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers. Br J Clin Pharmacol 1995; 40: 577–84PubMed Azizi M, Veyssier-Belot C, Alhenc-Gelas M, et al. Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers. Br J Clin Pharmacol 1995; 40: 577–84PubMed
41.
go back to reference Collignon F, Frydman A, Caplain H, et al. Comparison of the pharmacokinetic profiles of three low molecular mass heparins: dalteparin, enoxaparin and nadroparin: administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost 1995; 73: 630–40PubMed Collignon F, Frydman A, Caplain H, et al. Comparison of the pharmacokinetic profiles of three low molecular mass heparins: dalteparin, enoxaparin and nadroparin: administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost 1995; 73: 630–40PubMed
42.
go back to reference Eriksson BI, Soderberg K, Widlund L, et al. A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers. Thromb Haemost 1995; 73: 398–401PubMed Eriksson BI, Soderberg K, Widlund L, et al. A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers. Thromb Haemost 1995; 73: 398–401PubMed
43.
go back to reference Frydman AM, Bara L, Le Roux Y, et al. The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80mg. J Clin Pharmacol 1988; 28: 609–18PubMed Frydman AM, Bara L, Le Roux Y, et al. The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80mg. J Clin Pharmacol 1988; 28: 609–18PubMed
44.
go back to reference Bara L, Billaud E, Gramond G, et al. Comparative pharmacokinetics of a low molecular weight heparin (PK 10169) and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res 1985; 39: 631–6PubMedCrossRef Bara L, Billaud E, Gramond G, et al. Comparative pharmacokinetics of a low molecular weight heparin (PK 10169) and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res 1985; 39: 631–6PubMedCrossRef
45.
go back to reference Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost 2000; 26 Suppl. 1: 31–8PubMedCrossRef Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost 2000; 26 Suppl. 1: 31–8PubMedCrossRef
46.
go back to reference Bendetowicz AV, Beguin S, Caplain H, et al. Pharmacokinetics and pharmacodynamics of a low molecular weight heparin (enoxaparin) after subcutaneous injection, comparison with unfractionated heparin: a three way cross over study in human volunteers. Thromb Haemost 1994; 71: 305–13PubMed Bendetowicz AV, Beguin S, Caplain H, et al. Pharmacokinetics and pharmacodynamics of a low molecular weight heparin (enoxaparin) after subcutaneous injection, comparison with unfractionated heparin: a three way cross over study in human volunteers. Thromb Haemost 1994; 71: 305–13PubMed
47.
go back to reference Rabah MM, Premmereur J, Graham M, et al. Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris. Am J Cardiol 1999; 84: 1391–5PubMedCrossRef Rabah MM, Premmereur J, Graham M, et al. Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris. Am J Cardiol 1999; 84: 1391–5PubMedCrossRef
48.
go back to reference Laforest MD, Colas-Linhart N, Guiraud-Vitaux F, et al. Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers. Br J Haematol 1991; 77: 201–8PubMedCrossRef Laforest MD, Colas-Linhart N, Guiraud-Vitaux F, et al. Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers. Br J Haematol 1991; 77: 201–8PubMedCrossRef
49.
go back to reference Bara L, Samama M. Pharmacokinetics of low molecular weight heparins. Acta Chir Scand Suppl 1988; 543: 65–72PubMed Bara L, Samama M. Pharmacokinetics of low molecular weight heparins. Acta Chir Scand Suppl 1988; 543: 65–72PubMed
50.
go back to reference Boneu B, Caranobe C, Sie P. Pharmacokinetics of heparin and low molecular weight heparin. Baillieres Clin Haematol 1990; 3: 531–44PubMedCrossRef Boneu B, Caranobe C, Sie P. Pharmacokinetics of heparin and low molecular weight heparin. Baillieres Clin Haematol 1990; 3: 531–44PubMedCrossRef
51.
go back to reference Cadroy Y, Pourrat J, Baladre MF, et al. Delayed elimination of enoxaparin in patients with chronic renal insufficiency. Thromb Res 1991; 63: 385–90PubMedCrossRef Cadroy Y, Pourrat J, Baladre MF, et al. Delayed elimination of enoxaparin in patients with chronic renal insufficiency. Thromb Res 1991; 63: 385–90PubMedCrossRef
52.
go back to reference Eldor A. Thrombophilia, thrombosis and pregnancy. Thromb Haemost 2001; 86(1): 104–11PubMed Eldor A. Thrombophilia, thrombosis and pregnancy. Thromb Haemost 2001; 86(1): 104–11PubMed
53.
go back to reference Sanson BJ, Lensing AW, Prins MH, et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668–72PubMed Sanson BJ, Lensing AW, Prins MH, et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668–72PubMed
54.
go back to reference Casele HL, Laifer SA, Woelkers DA, et al. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol 1999; 181 (5 Pt 1): 1113–7PubMedCrossRef Casele HL, Laifer SA, Woelkers DA, et al. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol 1999; 181 (5 Pt 1): 1113–7PubMedCrossRef
55.
go back to reference Gibson JL, Ekevall K, Walker I, et al. Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin. Br J Obstet Gynaecol 1998; 105: 795–7PubMedCrossRef Gibson JL, Ekevall K, Walker I, et al. Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin. Br J Obstet Gynaecol 1998; 105: 795–7PubMedCrossRef
56.
go back to reference Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound. Thromb Res 1984; 34: 557–60PubMedCrossRef Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound. Thromb Res 1984; 34: 557–60PubMedCrossRef
57.
go back to reference Arcavi L, Maier A, Caspi A. Safety of enoxaparin in the geriatric population [abstract]. Eur Heart J 1999; 20 Suppl. 1: 285 Arcavi L, Maier A, Caspi A. Safety of enoxaparin in the geriatric population [abstract]. Eur Heart J 1999; 20 Suppl. 1: 285
58.
go back to reference Massicotte P, Adams M, Marzinotto V, et al. Low-molecular weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128: 313–8PubMedCrossRef Massicotte P, Adams M, Marzinotto V, et al. Low-molecular weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128: 313–8PubMedCrossRef
59.
go back to reference Punzalen RC, Hillery CA, Montgomery RR, et al. Low-molecular-weight heparin in thrombotic disease in children and adolescents. J Pediatr Hematol Oncol 2000; 22(2): 137–4CrossRef Punzalen RC, Hillery CA, Montgomery RR, et al. Low-molecular-weight heparin in thrombotic disease in children and adolescents. J Pediatr Hematol Oncol 2000; 22(2): 137–4CrossRef
60.
go back to reference Sanderink G, LeLiboux A, Jariwala N, et al. Enoxaparin pharmacokinetics and pharmacodynamics in renal impairment [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 229ACrossRef Sanderink G, LeLiboux A, Jariwala N, et al. Enoxaparin pharmacokinetics and pharmacodynamics in renal impairment [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 229ACrossRef
61.
go back to reference Bruno R, Vivier N, Veyrat-Follet C, et al. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel. Invest New Drugs 2001; 19: 163–9PubMedCrossRef Bruno R, Vivier N, Veyrat-Follet C, et al. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel. Invest New Drugs 2001; 19: 163–9PubMedCrossRef
62.
go back to reference Busby LT, Weyman A, Rodgers GM. Excessive anticoagulation in patients with mild renal insufficiency receiving long-term therapeutic enoxaparin. Am J Hematol 2001; 67(1): 54–6PubMedCrossRef Busby LT, Weyman A, Rodgers GM. Excessive anticoagulation in patients with mild renal insufficiency receiving long-term therapeutic enoxaparin. Am J Hematol 2001; 67(1): 54–6PubMedCrossRef
63.
go back to reference Gerlach AT, Pickworth KK, Seth SK, et al. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy 2000; 20(7): 771–5PubMedCrossRef Gerlach AT, Pickworth KK, Seth SK, et al. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy 2000; 20(7): 771–5PubMedCrossRef
64.
go back to reference Inverso SM, Cohen M, Antman EM, et al. Safety and efficacy of unfractionated heparin versus enoxaparin in obese patients and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 365ACrossRef Inverso SM, Cohen M, Antman EM, et al. Safety and efficacy of unfractionated heparin versus enoxaparin in obese patients and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 365ACrossRef
65.
go back to reference Follea G, Laville M, Pozet N, et al. Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chromic renal failure. Haemostasis 1986; 16: 147–51PubMed Follea G, Laville M, Pozet N, et al. Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chromic renal failure. Haemostasis 1986; 16: 147–51PubMed
66.
go back to reference Brophy DF, Wazny LD, Gehr TW, et al. The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease. Pharmacotherapy 2001; 21(2): 169–74PubMedCrossRef Brophy DF, Wazny LD, Gehr TW, et al. The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease. Pharmacotherapy 2001; 21(2): 169–74PubMedCrossRef
67.
go back to reference Przedlacki J, Bogdanska-Straszynska B, Sawicka B, et al. Antithrombotic activity of low molecular weight heparin (enoxaparin) during hemodialysis in patients with terminal kidney failure [in Polish]. Pol Arch Med Wewn 1993; 91: 438–45 Przedlacki J, Bogdanska-Straszynska B, Sawicka B, et al. Antithrombotic activity of low molecular weight heparin (enoxaparin) during hemodialysis in patients with terminal kidney failure [in Polish]. Pol Arch Med Wewn 1993; 91: 438–45
68.
go back to reference Sanderink G, LeLiboux A, Jariwala N, et al. Enoxaparin pharmacokinetics and pharmacodynamics in obese [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 229ACrossRef Sanderink G, LeLiboux A, Jariwala N, et al. Enoxaparin pharmacokinetics and pharmacodynamics in obese [abstract]. J Am Coll Cardiol 2001; 37(2) Suppl. A: 229ACrossRef
69.
go back to reference Cipolle RJ, Seifert RD, Neilan BA, et al. Heparin kinetics: variables related to disposition and dosage. Clin Pharmacol Ther 1981; 29: 387–93PubMedCrossRef Cipolle RJ, Seifert RD, Neilan BA, et al. Heparin kinetics: variables related to disposition and dosage. Clin Pharmacol Ther 1981; 29: 387–93PubMedCrossRef
70.
go back to reference Goodman SG, Cohen M, Bigonzi F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE study: efficacy and safety of subcutaneous enoxaparin in non-Q wave coronary events. J Am Coll Cardiol 2000; 36(3): 693–8PubMedCrossRef Goodman SG, Cohen M, Bigonzi F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE study: efficacy and safety of subcutaneous enoxaparin in non-Q wave coronary events. J Am Coll Cardiol 2000; 36(3): 693–8PubMedCrossRef
71.
go back to reference Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) IIB trial. Circulation 1999; 100: 1593–601PubMedCrossRef Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) IIB trial. Circulation 1999; 100: 1593–601PubMedCrossRef
72.
go back to reference The FRAX. I.S. Study Group. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. Eur Heart J 1999; 20: 1553–62CrossRef The FRAX. I.S. Study Group. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. Eur Heart J 1999; 20: 1553–62CrossRef
73.
go back to reference Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999; 354: 701–7CrossRef Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999; 354: 701–7CrossRef
74.
go back to reference Michalis LK, Papamichail N, Katsouras CS, et al. Enoxaparin versus tinzaparin in the management of unstable coronary artery disease (EVET Study) [abstract]. J Am Coll Cardiol 2001; 37(2): 365ACrossRef Michalis LK, Papamichail N, Katsouras CS, et al. Enoxaparin versus tinzaparin in the management of unstable coronary artery disease (EVET Study) [abstract]. J Am Coll Cardiol 2001; 37(2): 365ACrossRef
75.
go back to reference Zidar JP. Low-molecular-weight heparins in coronary stenting (the ENTICES trial): ENoxaparin and TIClopidine after Elective Stenting. Am J Cardiol 1998; 82: 29L–32LPubMedCrossRef Zidar JP. Low-molecular-weight heparins in coronary stenting (the ENTICES trial): ENoxaparin and TIClopidine after Elective Stenting. Am J Cardiol 1998; 82: 29L–32LPubMedCrossRef
76.
go back to reference Kereiakes DJ, Young J, Broderick TM, et al. Therapeutic adjuncts for immediate transfer to the catheterization laboratory in patients with acute coronary syndromes. Am J Cardiol 2000; 86 Suppl. 12B: 10M–7MPubMedCrossRef Kereiakes DJ, Young J, Broderick TM, et al. Therapeutic adjuncts for immediate transfer to the catheterization laboratory in patients with acute coronary syndromes. Am J Cardiol 2000; 86 Suppl. 12B: 10M–7MPubMedCrossRef
77.
go back to reference Young JJ, Kereiakes DJ, Grines CL, et al. Low-molecular weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 Trials. J Invasive Cardiol 2000; 12 Suppl. E: E14–8PubMed Young JJ, Kereiakes DJ, Grines CL, et al. Low-molecular weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 Trials. J Invasive Cardiol 2000; 12 Suppl. E: E14–8PubMed
78.
go back to reference Kereiakes DJ, Grines C, Fry E, et al. National investigators collaborating on enoxaparin: enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention. J Invasive Cardiol 2001; 13(4): 272–8PubMed Kereiakes DJ, Grines C, Fry E, et al. National investigators collaborating on enoxaparin: enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention. J Invasive Cardiol 2001; 13(4): 272–8PubMed
79.
go back to reference Planes A, Vochelle N, Mazas F, et al. Prevention of post-operative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988; 60: 407–10PubMed Planes A, Vochelle N, Mazas F, et al. Prevention of post-operative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988; 60: 407–10PubMed
80.
go back to reference The German Hip Arthroplasty Trial (GHAT) Group. Prevention of deep vein thrombosis with low molecular-weight heparin in patients undergoing total hip replacement: a randomized trial. Arch Orthop Trauma Surg 1992; 111(2): 110–20CrossRef The German Hip Arthroplasty Trial (GHAT) Group. Prevention of deep vein thrombosis with low molecular-weight heparin in patients undergoing total hip replacement: a randomized trial. Arch Orthop Trauma Surg 1992; 111(2): 110–20CrossRef
Metadata
Title
Pharmacodynamic and Pharmacokinetic Properties of Enoxaparin
Implications for Clinical Practice
Authors
Dr Jawed Fareed
Debra Hoppensteadt
Jeanine Walenga
Omer Iqbal
Qing Ma
Walter Jeske
Taqdees Sheikh
Publication date
01-10-2003
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 12/2003
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200342120-00003