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Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor

Vicagrel is a new antiplatelet pro-drug based on clopidogrel sulfur lactone metabolites. The purpose of the study was to evaluate the safety, tolerability, and pharmacodynamics (PD) of vicagrel in healthy Chinese subjects. This study was designed as a single-center, randomized, double-blind, placebo...

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Autores principales: Li, Hui, Chen, Hanjing, Chen, Weili, Xu, Hongrong, Yuan, Fei, Yang, Mengjie, Sun, Hongbin, Yang, Jin, Liu, Yongqiang, Lai, Xiaojuan, Gong, Yanchun, Liu, Xuefang, Li, Yongguo, Sheng, Lei, Liu, Chao, Li, Xuening
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004678/
https://www.ncbi.nlm.nih.gov/pubmed/31977858
http://dx.doi.org/10.1097/MD.0000000000018683
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author Li, Hui
Chen, Hanjing
Chen, Weili
Xu, Hongrong
Yuan, Fei
Yang, Mengjie
Sun, Hongbin
Yang, Jin
Liu, Yongqiang
Lai, Xiaojuan
Gong, Yanchun
Liu, Xuefang
Li, Yongguo
Sheng, Lei
Liu, Chao
Li, Xuening
author_facet Li, Hui
Chen, Hanjing
Chen, Weili
Xu, Hongrong
Yuan, Fei
Yang, Mengjie
Sun, Hongbin
Yang, Jin
Liu, Yongqiang
Lai, Xiaojuan
Gong, Yanchun
Liu, Xuefang
Li, Yongguo
Sheng, Lei
Liu, Chao
Li, Xuening
author_sort Li, Hui
collection PubMed
description Vicagrel is a new antiplatelet pro-drug based on clopidogrel sulfur lactone metabolites. The purpose of the study was to evaluate the safety, tolerability, and pharmacodynamics (PD) of vicagrel in healthy Chinese subjects. This study was designed as a single-center, randomized, double-blind, placebo-controlled, single oral ascending dose study. Fifty nine subjects were assigned to 6 vicagrel dose cohorts (5, 10, 20, 40, 60, and 75 mg), and 8 subjects were assigned to 75 mg clopidogrel. Within each vicagrel dose cohort, the 10 subjects (9 in the 75 mg cohort) were randomized 4:1 to receive vicagrel or placebo. Platelet function was assessed using VerifyNow(TM) P2Y12. ΔP2Y12 reaction units (ΔPRU) and percent inhibition platelet aggregation (%IPA) were used to evaluate the PD of vicagrel. Although the number of adverse events (AEs) increased with vicagrel dose, none were considered serious, suggesting that vicagrel is safe and well-tolerated. The ΔPRU and %IPA patterns suggest that inhibition of ADP-induced platelet aggregation increased in a dose-dependent manner across the 10 to 40 mg dose range. The inhibitory effect was nearly complete at 4 hours (mean %IPA 87.9%–93.0%, mean ΔPRU 206.6–240.0) for doses of 40 to 75 mg of vicagrel. In contrast, for 5 mg vicagrel and 75 mg clopidogrel, there were no measurable effects on platelet aggregation throughout the study. The results suggest that vicagrel at 40 to 75 mg inhibits ADP-induced platelet aggregation, with a fast onset of action and significantly greater potency than clopidogrel. These findings indicate that vicagrel may be a highly effective and well-tolerated antiplatelet agent.
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spelling pubmed-70046782020-02-18 Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor Li, Hui Chen, Hanjing Chen, Weili Xu, Hongrong Yuan, Fei Yang, Mengjie Sun, Hongbin Yang, Jin Liu, Yongqiang Lai, Xiaojuan Gong, Yanchun Liu, Xuefang Li, Yongguo Sheng, Lei Liu, Chao Li, Xuening Medicine (Baltimore) 4200 Vicagrel is a new antiplatelet pro-drug based on clopidogrel sulfur lactone metabolites. The purpose of the study was to evaluate the safety, tolerability, and pharmacodynamics (PD) of vicagrel in healthy Chinese subjects. This study was designed as a single-center, randomized, double-blind, placebo-controlled, single oral ascending dose study. Fifty nine subjects were assigned to 6 vicagrel dose cohorts (5, 10, 20, 40, 60, and 75 mg), and 8 subjects were assigned to 75 mg clopidogrel. Within each vicagrel dose cohort, the 10 subjects (9 in the 75 mg cohort) were randomized 4:1 to receive vicagrel or placebo. Platelet function was assessed using VerifyNow(TM) P2Y12. ΔP2Y12 reaction units (ΔPRU) and percent inhibition platelet aggregation (%IPA) were used to evaluate the PD of vicagrel. Although the number of adverse events (AEs) increased with vicagrel dose, none were considered serious, suggesting that vicagrel is safe and well-tolerated. The ΔPRU and %IPA patterns suggest that inhibition of ADP-induced platelet aggregation increased in a dose-dependent manner across the 10 to 40 mg dose range. The inhibitory effect was nearly complete at 4 hours (mean %IPA 87.9%–93.0%, mean ΔPRU 206.6–240.0) for doses of 40 to 75 mg of vicagrel. In contrast, for 5 mg vicagrel and 75 mg clopidogrel, there were no measurable effects on platelet aggregation throughout the study. The results suggest that vicagrel at 40 to 75 mg inhibits ADP-induced platelet aggregation, with a fast onset of action and significantly greater potency than clopidogrel. These findings indicate that vicagrel may be a highly effective and well-tolerated antiplatelet agent. Wolters Kluwer Health 2020-01-24 /pmc/articles/PMC7004678/ /pubmed/31977858 http://dx.doi.org/10.1097/MD.0000000000018683 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0
spellingShingle 4200
Li, Hui
Chen, Hanjing
Chen, Weili
Xu, Hongrong
Yuan, Fei
Yang, Mengjie
Sun, Hongbin
Yang, Jin
Liu, Yongqiang
Lai, Xiaojuan
Gong, Yanchun
Liu, Xuefang
Li, Yongguo
Sheng, Lei
Liu, Chao
Li, Xuening
Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title_full Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title_fullStr Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title_full_unstemmed Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title_short Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor
title_sort platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine p2y12 inhibitor
topic 4200
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004678/
https://www.ncbi.nlm.nih.gov/pubmed/31977858
http://dx.doi.org/10.1097/MD.0000000000018683
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