Pharmacokinetics and pharmacokinetic/pharmacodynamic relationship of vicagrel, a novel thienopyridine P2Y
Active metabolite
Clopidogrel
P2Y(12) inhibitor
Pharmacokinetics
Thienopyridine
Vicagrel
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
15 Jan 2019
15 Jan 2019
Historique:
received:
06
02
2018
revised:
31
08
2018
accepted:
11
10
2018
pubmed:
17
10
2018
medline:
16
4
2019
entrez:
17
10
2018
Statut:
ppublish
Résumé
Vicagrel, a novel thienopyridine antiplatelet agent, is an analogue of clopidogrel in development for the treatment of acute coronary syndromes. This study investigated the pharmacokinetic properties of vicagrel after single oral dosing with a direct comparison with clopidogrel in healthy Chinese subjects in the first two phase I clinical studies. The relationship between the exposure to the active metabolite and the platelet reactivity was also assessed for vicagrel. Study A was a single-ascending-dose study of vicagrel (5-75 mg) compared with clopidogrel (75 mg) in 67 healthy volunteers. Study B was a randomized, two-period, crossover, loading-dose study of vicagrel 20 mg compared with clopidogrel 300 mg in 12 healthy subjects. Plasma concentrations of three common metabolites of vicagrel and clopidogrel, the active thiol metabolite H4, the inactive thiol metabolite H3, and the S-methylated form of H3 (SM3, the major metabolite of vicagrel), were determined using a validated UHPLC-MS/MS method. The relationship between the AUC In the single-ascending-dose study, vicagrel was metabolized rapidly with the median t Vicagrel was rapidly and extensively metabolized, and the levels of the parent drug in circulation were very low. The pharmacokinetics of the three metabolites of vicagrel were linear and predictable across the dose range of 5-75 mg. The AUC of active H4 was apparently associated with the P2Y CTR20150346, CTR20160379.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Vicagrel, a novel thienopyridine antiplatelet agent, is an analogue of clopidogrel in development for the treatment of acute coronary syndromes. This study investigated the pharmacokinetic properties of vicagrel after single oral dosing with a direct comparison with clopidogrel in healthy Chinese subjects in the first two phase I clinical studies. The relationship between the exposure to the active metabolite and the platelet reactivity was also assessed for vicagrel.
METHODS
METHODS
Study A was a single-ascending-dose study of vicagrel (5-75 mg) compared with clopidogrel (75 mg) in 67 healthy volunteers. Study B was a randomized, two-period, crossover, loading-dose study of vicagrel 20 mg compared with clopidogrel 300 mg in 12 healthy subjects. Plasma concentrations of three common metabolites of vicagrel and clopidogrel, the active thiol metabolite H4, the inactive thiol metabolite H3, and the S-methylated form of H3 (SM3, the major metabolite of vicagrel), were determined using a validated UHPLC-MS/MS method. The relationship between the AUC
RESULTS
RESULTS
In the single-ascending-dose study, vicagrel was metabolized rapidly with the median t
CONCLUSIONS
CONCLUSIONS
Vicagrel was rapidly and extensively metabolized, and the levels of the parent drug in circulation were very low. The pharmacokinetics of the three metabolites of vicagrel were linear and predictable across the dose range of 5-75 mg. The AUC of active H4 was apparently associated with the P2Y
TRIAL REGISTRATION
BACKGROUND
CTR20150346, CTR20160379.
Identifiants
pubmed: 30326264
pii: S0928-0987(18)30458-5
doi: 10.1016/j.ejps.2018.10.011
pii:
doi:
Substances chimiques
Phenylacetates
0
Platelet Aggregation Inhibitors
0
Purinergic P2Y Receptor Antagonists
0
Thiophenes
0
methyl 2-(2-acetoxy-6,7-dihydrothieno(3,2-c)pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate
0
Clopidogrel
A74586SNO7
Types de publication
Comparative Study
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
151-160Informations de copyright
Copyright © 2018. Published by Elsevier B.V.