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DOI: 10.1055/s-0038-1653787
A Comparative Study of Three Low-molecular Weight Heparins (LMWH) and Unfractionated Heparin (UH) in Healthy Volunteers
Publikationsverlauf
Received29. April 1994
Accepted after revision 04. November 1994
Publikationsdatum:
09. Juli 2018 (online)
Summary
The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparations, show a high degree of variability. This variation has been proposed as correlated to the variation in incidence of postoperative deep vein thrombosis (DVT) (8-30%) in different LMWH studies on comparable populations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane® (enoxaparin), Fragmin® (dalteparin) and Logiparin® (tinzaparin), applying the concept of bioequivalence, although unknown which activity/activities are best correlated to efficacy. Unfractionated heparin (UH) was included in the study as a reference drug.
The drugs were studied with a cross-over technique in 12 healthy subjects and given subcutaneously in the doses recommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activities were measured using chromogenic substrate methods
The anti-Xa peak activity (Cmax) and the area under the curve (AUC) were highest for Clexane® and Fragmin® and lower for Logiparin® and UH. Clexane® and Fragmin® were considered bioequivalent in anti-Xa activity. Regarding anti-IIa activity, no bioequivalence was found between the products. Fragmin® was clearly different, with Cmax and AUC approximately twice as high as the other drugs. Whether the demonstrated differences in anti-Xa and anti-II activities are of any clinical significance remains unclear and can only be established by comparative clinical studies.
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References
- 1 Levine MN, Planes A, Hirsh J, Goodyear M, Vochelle N, Gent M. The relationship between anti-Factor Xa level and clinical outcome in patients receiving Enoxaparine LMWH to prevent deep vein thrombosis after hip replacement. Thromb Haemost 1989; 62: 940-944
- 2 Bara L, Leizorovicz A, Picolet H, Samama M. Correlation between anti-Xa and occurrence of thrombosis and haemorrhage in post-surgical patients treated with either Logiparin® (LMWH) or unfractionated heparin. Thromb Res 1992; 65: 641-650
- 3 Eriksson BI, Kälebo P, Anthmyr BA, Wadenvik H, Tengborn L, Risberg B. Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. J Bone and Joint Surgery 1991; 73 A (04) 484-93
- 4 Gray E, Padilla A, Barrowcliffe TW. Antithrombotic activity and its relationship to in vitro anticoagulant effects. Haemostasis 1993; 23 Suppl (Suppl. 01) 99-102
- 5 Wagenvoord RJ, Hendrix HH, Kolde HJ, Hemker HC. Development of a rapid and sensitive chromogenic heparin assay for clinical use. Haemostasis 1993; 23: 26-37
- 6 RØise O, Nurmohamed M, Reijnders P, Touzard R, Stiekema J, Bachman F, Bergqvist D, Büller H, Hirsh J, Magnani H. A multicenter randomised assessor-blind pilot study comparing the efficacy in the prophylaxis of DVT and the safety of Orgaran® (Org 10172), Fragmin®, Clexane®/Lovenox® in patients undergoing surgery for a fractured hip. Thromb Haemost 1993; 69: 620 (Abstr 273)
- 7 Nurmohamed MT, Rosendaal FR, Büller HR, Dekker E, Hommes DW, Vandenbroucke JP, Briöt E. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet 1992; 340: 152-156
- 8 Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D, Elliot G, Panju A, Brant R. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Eng J Med 1993; 329: 1370-1376
- 9 Commission of the European Communities, CPMP Working Party on Efficacy of Medicinal Products. Notes for Guidance. Investigation of Bioavail-ability and Bioequivalence, 111/ 54/ 89-EN 12/1991
- 10 Palm M, Wu H, Mattsson C, Ansari A. Pharmacokinetic properties of size homogenous oligosaccharides. Thromb Res 1990; 59: 799-805
- 11 Stiekema JC J, van Griesen JM T, van Dinther TG, Cohen AF. A cross-over comparison of the anti-clotting effects of three low molecular weight heparins and glycosaminoglycuronan. Br J Clin Pharm 1993; 36: 51-56
- 12 Bara L, Bloch MF, Zitoun D, Samama M, Collignon F, Frydman A, Uzan A, Bouthier J. 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: 443-452