Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers

Bratt, Göran; Törnebohm, E.; Widlund, L.; Lockner, D.

doi:10.1016/0049-3848(86)90340-3

Cited by 136 publications

(71 citation statements)

References 14 publications

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“…Thus a lower capacity to release LPL is not a sufficient explanation for the lower plasma LPL activity induced by low-Mr heparin, regardless of the findings on binding affinity in vitro. Low-Mr heparin itself is cleared less rapidly than conventional heparin from the circulation (Bratt et al, 1986;Dawes et al, 1986;Palm & Mattsson, 1987;Matzsch et al, 1987); hence, a more rapid decrease in circulating heparin cannot explain the lower plasma LPL activity.…”

Section: Discussionmentioning

confidence: 99%

“…This release results in rapid hydrolysis of lipoprotein triacylglycerols in the circulating blood, with generation of high levels of nonesterified fatty acids (Persson et al, 1985) and conversion of the lipoproteins into remnant particles. Preparations of low-Mr heparin have attracted attention because they have improved pharmacokinetic properties (higher bioavailability and longer half-life) than conventional heparin (Bratt et al, 1986;Maitzsch et al, 1987;HJolmer, 1989) and because they have similar antithrombotic activity as conventional heparin but in some animal models a lower tendency to cause bleeding (Carter & Kelton, 1982;Abdriuoli et al, 1985;Holmer, 1989). They have also been reported to possess lower lipolytic activity (Kakkar et al, 1982;Etienne et al, 1983;de Swart et al, 1984;Persson et al, 1985Persson et al, , 1987, which in turn results in lower plasma levels of nonesterified fatty acids (Persson et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Liu

Bengtsson‐Olivecrona

Østergaard

et al. 1991

Biochemical Journal

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This study compares a low-Mr heparin preparation with conventional heparin with respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects on the enzyme in vivo. Both heparin preparations were polydisperse in binding to LPL, but on average the low-Mr preparation showed lower affinity. Thus both conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr heparin was shifted towards lower salt concentrations. To displace LPL from immobilized heparin a higher concentration of low-Mr than of conventional heparin was needed. Injection of the low-Mr heparin into intact rats resulted in lower plasma LPL activity than did injection of an equal mass of conventional heparin, but when the liver was excluded from the circulation both heparin preparations resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin had at least the same effect on the release of LPL activity as did conventional heparin. In perfused livers, on the other hand, low-Mr heparin was less effective than conventional heparin in preventing the rapid uptake of exogenous labelled LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does not result in a demonstrably lower potency to release the enzyme from endothelial binding sites in peripheral tissues, but does result in a substantially decreased effect on the hepatic clearance of the enzyme.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Liu

Bengtsson‐Olivecrona

Østergaard

et al. 1991

Biochemical Journal

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“…Patients were then started on either intravenous unfractionated heparin (Heparin, Leo Pharmaceuticals, Princes Risborough, Bucks, U.K.) 1000 U/hour for 24 h (five male patients; mean age 59 years (range 49-66)) or 5000 units of low molecular weight heparin (Fragmin, Pharmacia and Upjohn, Milton Keynes, U.K.) subcutaneously twice daily for 24 h (six patients; five male, mean age 65 years (range 50-81)). The unfractionated heparin group were sampled at 24 h and the low molecular weight heparin group were sampled 4 h after the morning injection of low molecular weight heparin, coincident with the peak activity of the drug [16] . All patients gave written consent to participate in the studies, which were approved by the Ethical Practices Committee of the Royal Brompton Hospital.…”

Section: Unstable Angina Patients Receiving Heparinmentioning

confidence: 99%

Increased platelet responsiveness following coronary stenting Heparin as a possible aetiological factor in stent thrombosis

Knight

Panesar²,

Wilson³

et al. 1998

European Heart Journal

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“…Also LMWH have a longer plasma half-life [29,30] and a more favourable antithrombotic to haemorrhagic risk ratio; they maintain their antithrombotic effect prob ably through anti-Xa activity but cause less clinical bleeding by a reduced action on the APTT and overall clotting [28,31,32]. These properties might allow LMWH to be administered once daily without laboratory monitoring.…”

Section: Low Molecular Weight Heparins (Lmwh)mentioning

confidence: 99%

New developments in the treatment of deep venous thrombosis

Janssen¹,

Nováková²,

Verbruggen³

et al. 1997

The Netherlands Journal of Medicine

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An initial course of standard heparin (SH) or low-molecular-weight heparins (LMWH) is regarded as the treatment of choice for patients with deep venous thrombosis (DVT). LMWH have better bioavailability after subcutaneous administra tion, have a longer half-life, and show higher and more predictable anticoagulant activity. As a result they can be given subcutaneously and without laboratory control, using a dose that is determined by body weight. Because of these multiple advantages of LMWH they will replace SH in the future and subsequently home treatment with LMWH of selected patients seems feasible. The currently accepted approach is to start with SH or LMWH therapy combined with oral anticoagulant therapy (OAT) at the time of diagnosis. The course of SH or LMWH should continue for at least 5 days, provided that international normalized ratio (INR) is in the therapeutic range on 2 consecutive days. OAT should be continued for at least 3 months to prolong the prothrombin time to an INR of 2 -3 . When oral anticoagulants are either contraindicated or inconvenient, SH or LMWH can be used at the middosing interval. The role of anti-platelet treatment is not yet established 4 and should be compared with coumarin therapy in the future.

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Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers

Cited by 136 publications

References 14 publications

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Increased platelet responsiveness following coronary stenting Heparin as a possible aetiological factor in stent thrombosis

New developments in the treatment of deep venous thrombosis

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