No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects.
Summary of "No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects."
Vorapaxar, a novel antiplatelet agent in advanced clinical development for the prevention and treatment of atherothrombotic disease, is a potent, orally bioavailable thrombin receptor antagonist selective for the protease-activated receptor 1 (PAR-1).
Since race/ethnicity may affect the safety, efficacy and dosage of drugs, this study was conducted to evaluate potential differences in the pharmacodynamics, pharmacokinetics and safety of vorapaxar after single (5, 10, 20, or 40 mg) or multiple (0.5, 1, or 2.5 mg once daily) doses in healthy Japanese and matched (gender, age, height, and weight) Caucasian volunteers.
Vorapaxar was well tolerated in both Japanese and Caucasian subjects. Pharmacodynamic and pharmacokinetic profiles of vorapaxar in the two racial/ethnic groups were similar. In both racial groups, complete inhibition of platelet aggregation was achieved most rapidly with vorapaxar 40 mg and was consistently achieved and maintained with a 2.5 mg daily maintenance dose.
There were no substantial differences in the safety, pharmacokinetics or pharmacodynamics of vorapaxar between Japanese and Caucasian subjects.
Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA, email@example.com.
This article was published in the following journal.
Name: European journal of clinical pharmacology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21969227
- DOI: http://dx.doi.org/10.1007/s00228-011-1127-z
Medical and Biotech [MESH] Definitions
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.
Clotting time of PLASMA mixed with a THROMBIN solution. It is a measure of the conversion of FIBRINOGEN to FIBRIN, which is prolonged by AFIBRINOGENEMIA, abnormal fibrinogen, or the presence of inhibitory substances, e.g., fibrin-fibrinogen degradation products, or HEPARIN. BATROXOBIN, a thrombin-like enzyme unaffected by the presence of heparin, may be used in place of thrombin.
A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.
The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)
PURPOSE: The aim of our study was to evaluate the pharmacology of vorapaxar (SCH 530348), an oral PAR-1 antagonist, in healthy volunteers. METHODS AND RESULTS: In two randomized, placebo-controlled st...
PURPOSE: To determine whether impaired renal function alters the pharmacokinetics (PK) of vorapaxar or its ability to inhibit thrombin receptor agonist peptide (TRAP)-induced pla...
Background Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods In this multinational, double-blind, randomize...
Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with per...
Vorapaxar is the first substance of a new class of antiplatelet drugs that has been tested in large clinical trials. The protease-activated receptor 1 (PAR-1) antagonist inhibits thrombin-induced plat...
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