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.
