A COMPARATIVE-STUDY OF 3 LOW-MOLECULAR-WEIGHT HEPARINS (LMWH) AND UNFRACTIONATED HEPARIN (UH) IN HEALTHY-VOLUNTEERS

The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparati ons, show a high degree of variability. This variation has been propos ed as correlated to the variation in incidence of postoperative deep v ein thrombosis (DVT) (8-30%) in different LMWH studies on comparable p opulations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane(R) (enoxaparin), Fragmin(R) (dalteparin) and Logiparin(R) (tinzaparin), applying the concept of bi oequivalence, although unknown which activity/activities are best corr elated to efficacy. Unfractionated heparin (UH) was included in the st udy as a reference drug. The drugs were studied with a cross-over tech nique in 12 healthy subjects and given subcutaneously in the doses rec ommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activi ties were measured using chromogenic substrate methods. The anti-Xa pe ak activity (C-max) and the area under the curve (AUG) were highest fo r Clexane(R) and Fragmin(R) and lower for Logiparin; and UH. Clexane(R ) and Fragmin(R) were considered bioequivalent in anti-Xa activity. Re garding anti-IIa activity, no bioequivalence was found between the pro ducts. Fragmin(R) was clearly different, with C-max and AUC approximat ely twice as high as the other drugs. Whether the demonstrated differe nces in anti-Xa and anti-II activities are of any clinical significanc e remains unclear and can only be established by comparative clinical studies.