ArticlePharmaceutical research2014
Contributions of intestine and plasma to the presystemic bioconversion of vicagrel, an acetate of clopidogrel.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2YBritish journal of clinical pharmacology · 2020Trial
- Platelet inhibitory activity, tolerability, and safety of vicagrel, a novel thienopyridine P2Y12 inhibitor.Medicine · 2020Trial
- Hydrolytic Metabolism of Withangulatin A Mediated by Serum Albumin Instead of Common Esterases in Plasma.European journal of drug metabolism and pharmacokinetics · 2023Article
- Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity.Frontiers in nutrition · 2022Article
- Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists.Clinical pharmacokinetics · 2020Review
- Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Approach.Frontiers in pharmacology · 2020Article
- Enhanced responsiveness of platelets to vicagrel in IL-10-deficient mice through STAT3-dependent up-regulation of the hydrolase arylacetamide deacetylase in the intestine.British journal of pharmacology · 2019Article
- Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers.Frontiers in pharmacology · 2018Article
- A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory Effects of Antiplatelet Agents.Journal of veterinary internal medicine · 2018Article
- Arylacetamide Deacetylase Is Involved in Vicagrel Bioactivation in Humans.Frontiers in pharmacology · 2017Article
- Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel.Frontiers in pharmacology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the contributions of intestine and plasma to the presystemic bioconversion of vicagrel, and track its subsequent bioconversion to 2-oxo-clopidogrel in vivo and in vitro to rationalize the design of vicagrel, an acetate analogue of clopidogrel.
methodsThe concentration-time profiles of 2-oxo-clopidogrel and active metabolite (AM) in presystem and circulation system was determined in the cannulated rats. Also, the rat intestinal S9 and human intestinal microsomes were conducted to examine the formation of 2-oxo-clopidogrel and AM. Meanwhile, the esterases in plasma and intestinal fractions responsible for the bioconversion of vicagrel to 2-oxo-clopidogrel were screened by the esterase inhibition and recombinant esterases.
resultsThe intestine was responsible for the formation of 2-oxo-clopidogrel and AM in vivo and in vitro, where carboxylesterases 2 (CE2) contributed greatly to the vicagrel cleavage during absorption. Other related esterases in plasma were paraoxonases (PON), carboxylesterases 1 (CE1) and butyrylcholine esterases (BChE).
conclusionThe findings rationalized the prodrug design hypothesis that vicagrel could overcome the extensive invalid hydrolysis of clopidogrel by the hepatic CE1 but experience the extensive hydrolysis to 2-oxo-clopidogrel and subsequent oxidation to AM in the intestine. This also supported the theory of improved pharmacological activity through facilitated formation of 2-oxo-clopidogrel, thus warranting much needed future clinical pharmacokinetic studies of vicagrel.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.