%0 Journal Article
%T DT©\678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y12 antagonists
%A Barbara D. Christian
%A Bruce E. Markham
%A Dale A. Lauver
%A Dawn S. Kuszynski
%A Haoming Zhang
%A James P. Teuber
%A Matthew P. Bernard
%A Yuqing E. Chen
%J Archive of "Pharmacology Research & Perspectives".
%D 2019
%R 10.1002/prp2.509
%X The novel clopidogrel conjugate, DT©\678, is an effective inhibitor of platelets and thrombosis in preclinical studies. However, a comparison of the bleeding risk with DT©\678 and currently approved P2Y12 antagonists has yet to be determined. The objective of this study was to evaluate the bleeding tendency of animals treated with clopidogrel, ticagrelor, and DT©\678. Ninety©\one New Zealand white rabbits were randomized to one of 13 treatment groups (n = 7). Platelet activation was assessed by flow cytometry and light transmission aggregometry before and after the administration of various doses of DT©\678, clopidogrel, and ticagrelor. Tongue template bleeding times were also measured before and after drug treatment. Treatment with P2Y12 receptor antagonists caused a dose©\dependent reduction in markers of platelet activation (P©\selectin and integrin ¦ÁIIb¦Â3) and aggregation in response to adenosine diphosphate stimulation. At the same doses required for platelet inhibition, clopidogrel and ticagrelor significantly prolonged bleeding times, while DT©\678 did not. DT©\678 and the FDA©\approved P2Y12 antagonists clopidogrel and ticagrelor are effective inhibitors of platelet activation and aggregation. However, unlike clopidogrel and ticagrelor, DT©\678 did not prolong bleeding times at equally effective antiplatelet doses. The results suggest a more favorable benefit/risk ratio for DT©\678 and potential utility as part of a dual antiplatelet therapy regimen
%K animals
%K bleeding time
%K clopidogrel
%K platelets
%K purinergic P2Y receptor antagonists
%K thrombosis
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658415/