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Despite Pharmaceutical Equivalence, Generic Versions of Enoxaparin May Differ in Their Pharmacodynamic Actions. Potential Clinical Implications
Author(s) -
Jeske Walter,
Walenga Jeanine M,
Hoppensteadt Debra,
McGeehan Elizabeth,
Harenberg Job,
Ramacciotti Eduardo,
Fareed Jawed
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.832.6
Subject(s) - pharmacodynamics , potency , antithrombotic , pharmacology , low molecular weight heparin , pharmacokinetics , anticoagulant , enoxaparin sodium , chemistry , medicine , in vitro , heparin , biochemistry
This study compared available generic enoxaparins with the branded version (Sanofi‐Aventis) in various assays and investigated their pharmacokinetic/pharmacodynamic behavior in a primate model. Methods Cutenox, Lupenox, enoxaparin Sandoz and Lovenox were compared in terms of molecular weight profiling, NMR profile and in vitro anticoagulant activity. Groups of primates (n=8–10) were administered LMWH (1 mg/kg subcutaneously) and blood samples were drawn over a 24 hour period to measure pharmacodynamic effects. Antithrombotic and bleeding effects were studied in rat models of jugular vein clamping and tail transection, respectively. Complexation studies with PF4 were carried out using a SELDI‐MS method. Results Anti‐Xa potency ranged from 86–110 U/mg and anti‐IIa potency ranged from 27–35 U/mg. Mean molecular weight of these LMWHs ranged from 4.2–4.5 kDa. Despite comparable pharmaceutical profiles, some of these products showed differences in the pharmacodynamic effects in terms of TFPI release, TAFI modulation, thrombin generation inhibition and protamine neutralization. Conclusion Although the generic enoxaparins are pharmaceutically equivalent, their pharmacodynamic profiles differ from the branded product. Thus, each generic product should be considered as a distinct LMWH and individual safety/efficacy data should be considered prior to its clinical use.