Key result
Vicagrel matches prasugrel antiplatelet potency with ~6-fold higher bioavailability than clopidogrel in rats.
Why the study?
Clopidogrel resistance limits its antiplatelet efficacy, necessitating development of more potent agents with improved bioavailability and effectiveness.
Does vicagrel improve bioavailability and antiplatelet potency compared to clopidogrel in preclinical models?
Does vicagrel improve bioavailability and antiplatelet potency compared to clopidogrel in preclinical models?
Vicagrel is a novel prodrug that demonstrates higher bioavailability and potency than clopidogrel in preclinical models, potentially overcoming CYP2C19-related resistance.
Promising potency supports further preclinical development; leaves open clinical utility against clopidogrel resistance.
A series of optically active 2-hydroxytetrahydrothienopyridine derivatives were designed and synthesized as prodrugs of clopidogrel thiolactone in order to overcome clopidogrel resistance. The final compounds were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. Compound 9a was selected for further in vitro and in vivo metabolism studies, since its potency was comparable to that of prasugrel and was much higher than that of clopidogrel. Preliminary pharmacokinetic study results showed that the bioavailability of clopidogrel thiolactone generated from 9a was 6-fold higher than that generated from clopidogrel, implying a much lower clinically effective dose for 9a in comparison with clopidogrel. In summary, 9a (vicagrel) holds great promise as a more potent and a safer antiplatelet agent that might have the following advantages over clopidogrel: (1) no drug resistance for CYP2C19 poor metabolizers; (2) lower dose-related toxicity due to a much lower effective dose; (3) faster onset of action.
No takes yet. Share an insight, caveat, or question.
Shan et al. (2012) studied Clopidogrel resistance. Vicagrel (Compound 9a) vs. Clopidogrel and prasugrel was evaluated on Inhibitory effect on ADP-induced platelet aggregation and bioavailability. Vicagrel (Compound 9a) demonstrated comparable antiplatelet potency to prasugrel and 6-fold higher bioavailability of the active thiolactone metabolite compared to clopidogrel in rats.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: