Relationship between Biological Activity and Concentration of a Low-Molecular-Weight Heparin (PK 10169) and Unfractionated Heparin after Intravenous and Subcutaneous Administration

Dawes, J.; Bara, L.; Samama, M

doi:10.1159/000215281

Cited by 52 publications

(61 citation statements)

References 15 publications

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“…Since polysulfates are primarily known for their anticoagulant activity and are used clinically for this purpose, a bioassay could, in principle, be based on the measure-ment of this anticoagulant activity (Dawes et al, 1986). Using this procedure, the plasma half-life of heparin in humans has been found to be approximately 35 min (after iv injection of 23 mg heparin) (Dawes et al, 1986).…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Witvrouw¹,

Desmyter²,

Clercq

1994

Antivir Chem Chemother

101

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Polysulfates are highly potent and selective inhibitors of the in vitro replication of HIV and other enveloped viruses. They not only inhibit the cytopathic effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation. They also act synergistically with other anti-HIV drugs. The anti-HIV activity of polysulfates is a result of their shielding of the positively charged sites in the V3 loop of the viral envelope glycoprotein gp120. When polysulfates were administered intravenously to rabbits, their half-life was approximately 2h. Although they are very poorly absorbed following oral administration, they can be made orally bioavailable with the appropriate chemical modifications. Also, polysulfates may lose (much of) their anticoagulant activity upon chemical modification without giving up their anti-HIV activity. Their efficacy in the therapy and/or prophylaxis of retroviral infections remains to be demonstrated both in animal models and in humans.

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Section: Pharmacokinetic Profilementioning

confidence: 99%

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Witvrouw¹,

Desmyter²,

Clercq

1994

Antivir Chem Chemother

101

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“…4,10 LMWHs have been used increasingly over the past few years, primarily for the prevention and treatment of venous thromboembolism. 11 However, recent evidence indicates that LMWHs are safe and effective antithrombotic agents for arterial thrombotic diseases.…”

mentioning

confidence: 99%

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

Leadley¹,

Kasiewski²,

Bostwick³

et al. 1998

ATVB

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Abstract-Experiments were designed to compare the antithrombotic efficacy of enoxaparin and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow reductions (CFRs) in the stenosed canine circumflex coronary artery. Low-molecular-weight heparins (LMWHs) are safe and effective in the prevention and treatment of venous thromboembolism. The present experiments were designed to evaluate the potential use of LMWHs in arterial thrombotic indications by comparing the antithrombotic effect of an LMWH with that of UH in an animal model of unstable angina. After establishment of consistent CFRs by experimentally induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was administered intravenously as a loading dose plus a continuous infusion for 1 hour. The inhibition of CFRs was taken as an indicator of antithrombotic efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose-dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kgϩ5 g/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9 to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase (NS) in template bleeding time. Near-complete abolishment of CFRs was achieved with enoxaparin at 1.0 mg/kgϩ10 g/kg per minute. This dose of enoxaparin produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL, an increase in APTT of 1.4-to 1.5-fold over baseline, and a 1.9-fold increase (PϽ0.05) in template bleeding time. In contrast, UH had no significant effect on CFRs at a dose (100 U/kgϩ10 U/kg per minute) that resulted in anti-Xa levels of 1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT greater than 10-fold over baseline, and a 2.

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“…LMWH have a number of advantages over SH: because there is less protein binding of LMWH [28], they have a more predictable anticoagulant response when administered in fixed doses, so the dose only has to be adjusted to the patient's body weight. 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].…”

Section: Low Molecular Weight Heparins (Lmwh)mentioning

confidence: 99%

“…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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Relationship between Biological Activity and Concentration of a Low-Molecular-Weight Heparin (PK 10169) and Unfractionated Heparin after Intravenous and Subcutaneous Administration

Cited by 52 publications

References 15 publications

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Inhibition of Repetitive Thrombus Formation in the Stenosed Canine Coronary Artery by Enoxaparin, But Not by Unfractionated Heparin

New developments in the treatment of deep venous thrombosis

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