PMID- 31977858
OWN - NLM
STAT- MEDLINE
DCOM- 20200210
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 99
IP  - 4
DP  - 2020 Jan
TI  - Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel 
      thienopyridine P2Y12 inhibitor.
PG  - e18683
LID - 10.1097/MD.0000000000018683 [doi]
LID - e18683
AB  - 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 P2Y12. DeltaP2Y12 reaction units (DeltaPRU) 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 DeltaPRU 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 DeltaPRU 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.
FAU - Li, Hui
AU  - Li H
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Chen, Hanjing
AU  - Chen H
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Chen, Weili
AU  - Chen W
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Xu, Hongrong
AU  - Xu H
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Yuan, Fei
AU  - Yuan F
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Yang, Mengjie
AU  - Yang M
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Sun, Hongbin
AU  - Sun H
AD  - State Key Laboratory of Natural Medicines and Center of Drug Discovery, College 
      of Pharmacy.
FAU - Yang, Jin
AU  - Yang J
AD  - Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University.
FAU - Liu, Yongqiang
AU  - Liu Y
AD  - Jiangsu Vcare PharmaTech Co. Ltd., Nanjing.
FAU - Lai, Xiaojuan
AU  - Lai X
AD  - Jiangsu Vcare PharmaTech Co. Ltd., Nanjing.
FAU - Gong, Yanchun
AU  - Gong Y
AD  - Jiangsu Vcare PharmaTech Co. Ltd., Nanjing.
FAU - Liu, Xuefang
AU  - Liu X
AD  - Jiangsu Vcare PharmaTech Co. Ltd., Nanjing.
FAU - Li, Yongguo
AU  - Li Y
AD  - Hua Medicine (Shanghai) Ltd., Shanghai China.
FAU - Sheng, Lei
AU  - Sheng L
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Liu, Chao
AU  - Liu C
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
FAU - Li, Xuening
AU  - Li X
AD  - Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 
      Shanghai.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Phenylacetates)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Thiophenes)
RN  - 0 (methyl 
      2-(2-acetoxy-6,7-dihydrothieno(3,2-c)pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate)
RN  - A74586SNO7 (Clopidogrel)
SB  - IM
MH  - Adult
MH  - Clopidogrel/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Phenylacetates/administration & dosage/adverse effects/*pharmacology
MH  - Platelet Activation/drug effects
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/administration & dosage/adverse 
      effects/*pharmacology
MH  - Platelet Function Tests
MH  - Thiophenes/administration & dosage/adverse effects/*pharmacology
MH  - Young Adult
PMC - PMC7004678
COIS- The authors have no conflicts of interests to disclose.
EDAT- 2020/01/25 06:00
MHDA- 2020/02/11 06:00
PMCR- 2020/01/24
CRDT- 2020/01/25 06:00
PHST- 2020/01/25 06:00 [entrez]
PHST- 2020/01/25 06:00 [pubmed]
PHST- 2020/02/11 06:00 [medline]
PHST- 2020/01/24 00:00 [pmc-release]
AID - 00005792-202001240-00017 [pii]
AID - MD-D-19-04955 [pii]
AID - 10.1097/MD.0000000000018683 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2020 Jan;99(4):e18683. doi: 10.1097/MD.0000000000018683.