Population pharmacokinetics of enoxaparin during the antenatal period
BACKGROUND: The optimal dosing strategy of low-molecular-weight heparins for the treatment of antenatal venous thromboembolism is not known. The physiological changes associated with pregnancy alter the pharmacokinetic profile of low-molecular-weight heparins, which has led to controversy and subsequent variation in practice, when pregnant women with venous thromboembolism are treated with low-molecular-weight heparins. Our objective was to develop a robust pharmacokinetic model of enoxaparin during the antenatal period to address this problem.
METHOD AND RESULTS: Women prescribed antenatal enoxaparin were eligible to enroll in the study. Recruited women were reviewed monthly and had up to 3 anti-Xa activities (trough and 1 and 3 hours after dose) drawn at each clinic attendance. Compartmental pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling. One hundred twenty-three patients contributed 795 anti-Xa activities for pharmacokinetic modeling purposes. Both enoxaparin clearance and volume of distribution were increased during pregnancy. Simulations of once- versus twice-daily enoxaparin administration demonstrated that both dosing regimens would reach target 3-hour plasma concentrations throughout the duration of the pregnancy. When trough anti-Xa activity was simulated, both once- and twice-daily regimens exhibited an increase in trough anti-Xa activity with the progression of pregnancy. This is explained by the significant increase in volume of distribution observed during pregnancy.
CONCLUSIONS: The half-life of enoxaparin is prolonged with the progression of pregnancy, and our work provides compelling evidence for prescribing once-daily enoxaparin for the treatment of antenatal venous thromboembolism. National and international guideline recommendations should be reconsidered.
| Errataetall: |
CommentIn: Nat Rev Cardiol. 2013 Oct;10(10):552-3. - PMID 23979212 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:128 |
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| Enthalten in: |
Circulation - 128(2013), 13 vom: 24. Sept., Seite 1462-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Patel, Jignesh P [VerfasserIn] |
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| Links: |
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| Themen: |
Anticoagulants |
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| Anmerkungen: |
Date Completed 25.11.2013 Date Revised 24.09.2013 published: Print-Electronic CommentIn: Nat Rev Cardiol. 2013 Oct;10(10):552-3. - PMID 23979212 Citation Status MEDLINE |
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| doi: |
10.1161/CIRCULATIONAHA.113.003198 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a CommentIn: Nat Rev Cardiol. 2013 Oct;10(10):552-3. - PMID 23979212 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: The optimal dosing strategy of low-molecular-weight heparins for the treatment of antenatal venous thromboembolism is not known. The physiological changes associated with pregnancy alter the pharmacokinetic profile of low-molecular-weight heparins, which has led to controversy and subsequent variation in practice, when pregnant women with venous thromboembolism are treated with low-molecular-weight heparins. Our objective was to develop a robust pharmacokinetic model of enoxaparin during the antenatal period to address this problem | ||
| 520 | |a METHOD AND RESULTS: Women prescribed antenatal enoxaparin were eligible to enroll in the study. Recruited women were reviewed monthly and had up to 3 anti-Xa activities (trough and 1 and 3 hours after dose) drawn at each clinic attendance. Compartmental pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling. One hundred twenty-three patients contributed 795 anti-Xa activities for pharmacokinetic modeling purposes. Both enoxaparin clearance and volume of distribution were increased during pregnancy. Simulations of once- versus twice-daily enoxaparin administration demonstrated that both dosing regimens would reach target 3-hour plasma concentrations throughout the duration of the pregnancy. When trough anti-Xa activity was simulated, both once- and twice-daily regimens exhibited an increase in trough anti-Xa activity with the progression of pregnancy. This is explained by the significant increase in volume of distribution observed during pregnancy | ||
| 520 | |a CONCLUSIONS: The half-life of enoxaparin is prolonged with the progression of pregnancy, and our work provides compelling evidence for prescribing once-daily enoxaparin for the treatment of antenatal venous thromboembolism. National and international guideline recommendations should be reconsidered | ||
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| 700 | 1 | |a Davies, J Graham |e verfasserin |4 aut | |
| 700 | 1 | |a Arya, Roopen |e verfasserin |4 aut | |
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