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Generic versions of argatroban can be differentiated from branded argatroban using a thrombin generation assay (TGA)
Author(s) -
Adiguzal Cafer,
Litinas Evangelos,
Cunanan Josephine,
Hoppensteadt Debra,
Fareed Jawed
Publication year - 2009
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.23.1_supplement.575.1
Subject(s) - argatroban , thrombin , potency , pharmacology , chemistry , discovery and development of direct thrombin inhibitors , fibrin , proteases , thrombin generation , biochemistry , in vitro , platelet , medicine , immunology , enzyme
Beside direct inhibition of thrombin, argatroban inhibits tissue factor mediated generation of proteases such as thrombin and Xa and the resultant formation of fibrin. Since generic and branded argatrobans have different thrombin inhibitory potencies, we hypothesized that differences in thrombin generation inhibition may also be observed. To test this hypothesis, we used the TECHNOTHROMBIN TGA assay to measure thrombin generation in platelet poor plasma (PPP) and platelet rich plasma (PRP) supplemented with argatrobans (branded and three generics: slovastan, gartban, and argaron) at concentrations from 0.6 to 5 µg/ml. Activators containing tissue factor and phospholipids at varying concentrations were used to generate thrombin. The order of inhibitory potency in PPP was argatroban> gartban> slovastan. All of the generic products showed stronger thrombin generation inhibition in PPP in comparison to argatroban. In PRP, there was a much wider difference among the generic argatrobans and order of potency was slovastan> gartban> argaron. In the fibrinokinetic assays wider differences were noted between generic and branded products; rank order was gartban> slovastan > argaran> branded argatroban. These observations underscore the differences between the generic and branded products and suggest that beside thrombin inhibitory assays argatroban can be differentiated in other biologic assays.