Pharmacoequivalence of Enoxaparin and Contaminated Enoxaparin

The use of heparin contaminated with oversulfated chondroitin sulfate (OSCS) was associated with adverse reactions. Some batches of enoxaparin also contained low levels of OSCS. Studies were performed to address the bioequivalence of enoxaparin and its contaminated version. Contaminant‐free (CFE) and contaminated enoxaparin (CCE) were administered subcutaneously to rats. Blood pressure and heart rate were measured 90 min. post‐administration, followed by jugular vein clamping model 120 min. post‐administration. Blood was collected to measure anticoagulant and anti‐protease effects. No differences in blood pressure or heart rate were observed between the two groups. Compared to saline treated rats (3.5±0.5 clampings), CCE and CFE treated animals required more clampings to induce thrombosis (4.8±0.7 and 5.0±0.6, respectively; p =0.001 vs. saline). The aPTT was slightly elevated in both CFE and CCE treated groups (CFE: 36.8±18.6 sec; CCE: 30.5±10.9 sec vs. saline: 26.7±3.9 sec). Anti‐Xa activity was significantly higher with CFE (84.4±1.5% inhibition) compared to CCE (80.5±2.9 % inhibition; p =0.026) while anti‐IIa activity was comparable (37.1±22.0 and 30.6±17.9 % inhibition). At <5%, OSCS does not impact the anti‐thrombotic effects enoxaparin. The impact of repeated administration of contaminated enoxaparins and long‐term pharmacodynamic and immunogenic effects needs to be explored further.