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Molecular Profiling of Generic Versions of the Low Molecular Weight Heparin Enoxaparin and Their Digestion by Heparinase-I.

Melanie Clark, He Zhu, Debra Hoppensteadt and Jawed Fareed
Pathology, Loyola University Medical Center, Maywood, IL

ABSTRACT

Generic versions of the low molecular weight heparin (LMWH) enoxaparin (Lovenox, Sanofi-Aventis, Bridgewater NY) are available in Southeast Asia and South America. The purpose of this study was to compare Lovenox with two generic versions, Lupenox (co. name) and Loparin (co. name). The molecular weight (MW) profile of these agents and unfractionated heparin (UFH) was determined using HPLC prior to and after heparinase-I digestion. The MW of the generic versions of LMWH ranged from 3.9 to 4.7 kDa. Lupenox exhibited the lowest mean MW (3.9 kDa), whereas Loparin was 4.7 kDa. UFH had a MW of 17.1 kDa. Heparinase-I digestion resulted in marked decrease in the MW of all agents studied. UFH was the most susceptible to the actions of heparinase-I digestion (> 50% reduction in MW) whereas the LMWHs exhibited a 20–30% reduction. Loparin was more susceptible to heparinase-I digestion (30%) compared to Lovenox and Lupenox. The molecular components with a MW > 7.5 kDa ranged from 3–10% for the LMWHs and >90% for UFH. The molecular components with a MW < 7.5 kDa ranged from 90 to 97% for LMWHs and 9% for UFH. These results suggest that the generic versions of LMWHs exhibit differences in their molecular profile and digestion by heparinase-I. Moreover the studies indicate that relative to UFH, both generic and branded enoxaparins are less susceptible to heparinase-I digestion.