Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy elderly volunteers.

Stiekema, J. C. J.; Wijnand, Herman P.; Dinther, T. G. Van; Moelker, H. C. T.; Dawes, J.; Vinchenzo, A.; Toeberich, H.

doi:10.1111/j.1365-2125.1989.tb05333.x

Cited by 42 publications

(10 citation statements)

References 19 publications

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“…treatment of Org 10172 and acenocoumarol was compared with administration of Org 10172 alone, no significant effects were seen in the concentrations of fibrinogen, AT-III, and the coagulation factors II, VII and X. The results of the pharmacokinetic analysis of the plasma anti-Xa, anti-IIa and TGI ac tivities are in agreement with previous phar macokinetic studies [7,8]. Acenocoumarol apparently does not in fluence, except for a small (10%) but signifi cant reduction of the clearance of plasma anti-Xa activity, the pharmacokinetic pa rameters of plasma anti-Xa and anti-IIa ac tivity.…”

Section: Discussionsupporting

confidence: 80%

Interaction of the Combined Medication with the New Low-Molecular-Weight Heparinoid Lomoparan® (Org 10172) and Acenocoumarol

Jc¹,

Danhof

et al. 1990

Pathophysiol Haemos Thromb

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A high intravenous dose of the low-molecular-weight heparinoid Lomoparan® (Org 10172) was administered to 6 healthy males in a steady state of anticoagulation (Thrombotest) by acenocoumarol. Prothrombin time, activated partial thromboplastin time and Stypven time were prolonged to a degree which was greater than that expected on the base of the summation of the effects by each drug alone. This effect was observed for a period of up to 1 h. The Thrombotest was affected for up to 5 h after the intravenous administration of Org 10172, therefore it is deemed unsuitable for monitoring the combined effects of these two anticoagulants during this period. Acenocoumarol did not affect the pharmacokinetic parameters of Org 10172 with the exception of a slight reduction of the clearance of plasma anti-Xa activity.

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Section: Discussionsupporting

confidence: 80%

Interaction of the Combined Medication with the New Low-Molecular-Weight Heparinoid Lomoparan® (Org 10172) and Acenocoumarol

Jc¹,

Danhof

et al. 1990

Pathophysiol Haemos Thromb

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“…These findings correlated with the diminished creatinine clearance associated with aging, indicating that age‐associated reductions in renal function warrant for monitoring anti‐FXa activity when LMWH is employed in the elderly [50]. A similar age‐related difference was not found for heparinoid Org 10172 (Danaparoid) [51].…”

Section: Age‐associated Bleeding Riskmentioning

confidence: 91%

Challenges in the prevention of venous thromboembolism in the elderly

Minno

Tufano

2004

Journal of Thrombosis and Haemostasis

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Summary. Aging itself is a risk factor for venous thromboembolism, and the prevalence in the elderly of additional risk factors (e.g. cancer, orthopedic surgery, immobility) increase its intrinsic risk. Many in the medical community are reluctant to prescribe anticoagulation (for primary and secondary prevention of venous thromboembolism) to their geriatric patients for the fear that bleeding complications may outweigh the benefits. A thorough analysis of the data support the concept that the under-use of heparin in primary prevention in the elderly is more related to medical beliefs than to facts. The risk of bleeding due to oral anticoagulants (secondary prevention) is greatly reduced by keeping the International Normalized Ratio (INR) values within therapeutic ranges and carefully avoiding conditions/drugs that may interfere with such treatment. The oral direct thrombin inhibitor ximelagatran has been studied for primary (hip and knee replacement surgery) and for secondary prophylaxis of venous thromboembolism, and for acute venous thromboembolism treatment. The selective factor Xa inhibitor fondaparinux has been approved for primary prophylaxis of venous thromboembolism in hip and knee replacement surgery and in hip fracture surgery. Studies on the latter drugs, where most of the patients were > 65 years of age, further show that the fear of bleeding complications due to anticoagulation in the elderly is largely unjustified.

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“…All drugs used in this study have been shown to be effective in the prophylaxis of deep venous thrombosis (DVT) and in one report a LMW heparin was found to be more effective than heparin, while the bleeding risk was reduced [6]. The half-lives of plasma anti-Xa activity after LMW heparins and Orgaran® in healthy volunteers were found to be considerably longer than that after standard heparin and they show improved bioavailability Introduction with respect to effect on clotting factors after subcutaneous administration [2,3,7]. The time-curves of the effects of different low molecular weight heparins and Orgaran® have been described previously but comparisons are difficult because different assays and reference standards have been used [8].…”

mentioning

confidence: 99%

A cross‐over comparison of the anti‐clotting effects of three low molecular weight heparins and glycosaminoglycuronan.

Stiekema¹,

Griensven²,

Dinther³

et al. 1993

Brit J Clinical Pharma

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1. The anti‐clotting effects after intravenous administration of three low molecular weight (LMW) heparins, Fragmin (KABI 2165), Fraxiparine (CY 216), Clexane (PK 10169) and the LMW mixture of glycosaminoglycuronans Orgaran (Org 10172) were compared in a randomized cross‐over study in 12 healthy male volunteers. 2. The time courses of the anti‐Xa activity of Fragmin, Fraxiparine and Clexane (five subjects) were best fitted by a monoexponential function and had comparable half‐lives of 1.9 h, 2.3 h and 2.8 h, respectively. The time courses of the anti‐Xa activity of Orgaran and Clexane (four subjects) were described by a biexponential function with terminal half‐lives of 56.8h and 27.7 h, respectively. They were longer than those of Fraxiparine and Fragmin. Orgaran injection was associated with a significantly smaller 'clearance' (0.8 +/‐ 0.2 l h‐1) of the plasma anti‐Xa activity compared with Fragmin (2.0 +/‐ 0.5), Fraxiparine (1.7 +/‐ 0.5) and Clexane (1.6 +/‐ 0.5). 3. In comparison with the three LMW heparins, the terminal half‐life of plasma anti‐IIa activity after Orgaran was longer and the 'clearance' of Orgaran was lower than that after Clexane. The area under the curve of the plasma anti‐IIa activity after administration of Orgaran was negligible compared with that obtained after injection of the LMW heparins. 4. Orgaran caused the smallest and Fragmin the greatest prolongation of the activated partial thromboplastin time (Orgaran 5.8 +/‐ 1.2 s vs Fragmin 18.5 +/‐ 5.2 s) and the thrombin clotting time (Orgaran 2.9 +/‐ 1.7 s vs Fragmin 47.8 +/‐ 0.9 s).(ABSTRACT TRUNCATED AT 250 WORDS)

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Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy elderly volunteers.

Cited by 42 publications

References 19 publications

Interaction of the Combined Medication with the New Low-Molecular-Weight Heparinoid Lomoparan® (Org 10172) and Acenocoumarol

Interaction of the Combined Medication with the New Low-Molecular-Weight Heparinoid Lomoparan® (Org 10172) and Acenocoumarol

Challenges in the prevention of venous thromboembolism in the elderly

A cross‐over comparison of the anti‐clotting effects of three low molecular weight heparins and glycosaminoglycuronan.

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