Delving into the Latest Updates on Vestipitant Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Vestipitant mesylate (USAN)

+ [3]

Target

NK1R

Action

antagonists

Mechanism

NK1R antagonists(Neurokinin 1 receptor antagonists)

Therapeutic Areas

Nervous System DiseasesDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Anxiety DisordersDepressive Disorder, MajorDyspepsia+ [4]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Accenture Plc

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC24H28F7N3O4S

InChIKeyBHECXGHXWKHZOY-DXPOFMJKSA-N

CAS Registry334476-64-1

This work describes a simple, sensitive and fast liquid chromatographic method using ultraviolet (UV) detection for the quantitation of Captisol™ (sulfobutyl ether-β-cyclodextrin, SBE-β-CD) in Vestipitant (GW597599) IV formulation. The chromatographic system consists of a cyano-modified silica stationary phase column with 0.5mM copper(II) acetate in 50/50 (v/v) water/acetonitrile and 0.05% (v/v) of trifluoroacetic acid as the mobile phase. Due to the fact that SBE-β-CD does not possess a chromophore suitable for UV detection, copper(II) acetate is used as a detection reagent. At low pH copper(II) acetate interacts with SBE-β-CD and produces mixed copper(II) [Cu(2+)] chelate and copper(II) mono acetate [CuOAc(+)] complexes, while displacing sodium ions [Na(+)] from the sulfobutyl ether (SBE) group. The copper(II)-SBE-β-CD interaction has optical properties that allow its detection by UV. This novel method is highly reproducible and reliable for accurate quantitation of SBE-β-CD content in the Vestipitant IV solution, and in the solution without the Vestipitant matrix.

01 Mar 2015·British Journal of AnaesthesiaQ1 · MEDICINE

Comparison of vestipitant with ondansetron for the treatment of breakthrough postoperative nausea and vomiting after failed prophylaxis with ondansetron

Q1 · MEDICINE

Article

Author: Russ, S F ; Novikova, E ; Noble, R ; Thompson, J P ; Brigandi, R A ; Kranke, P ; Eberhart, L H ; Johnson, B M ; Dalby, P L

BACKGROUNDPostoperative nausea and vomiting (PONV) is common; ondansetron is often used as prophylaxis or for breakthrough episodes. Vestipitant is a neurokinin 1 (NK-1) receptor antagonist that is effective for prophylaxis, but its efficacy for treating established PONV is unknown. This study was performed to evaluate the efficacy and safety of vestipitant, compared with ondansetron for the treatment of breakthrough PONV in patients who had already received prophylactic ondansetron before surgery.METHODSA multicentre, randomized, single-blind (sponsor-open), parallel group study. Of 527 surgical patients, 130 (25%) had breakthrough PONV and were equally randomized to one of six i.v. doses of vestipitant (4-36 mg) or ondansetron 4 mg. The primary endpoint was the rate of patients exhibiting complete response, defined as no emesis and no further rescue medication from 10 min after infusion up to 24 h after surgery or hospital discharge.RESULTSAll doses of vestipitant were non-inferior to ondansetron in treating PONV after failed prophylaxis with ondansetron. However, vestipitant was superior to ondansetron in decreasing episodes of postoperative emesis and retching. The complete response rate analysis using Bayesian model averaging indicated that no vestipitant dose was superior to ondansetron. Nausea numerical rating scale scores and the times-to-PONV or discharge were similar between the vestipitant and ondansetron treatment groups.CONCLUSIONSAlthough overall efficacy was non-inferior between vestipitant and ondansetron, the rate of emesis was lower with vestipitant. These data suggest that vestipitant may be a useful agent for the management of PONV, similar to other NK-1 antagonists.CLINICAL TRIAL REGISTRATIONNCT01507194.

01 Mar 2015·Clinical Pharmacology in Drug Development

Intravenous pharmacokinetics, local tolerability, and hemolysis of an SBE7‐β‐cyclodextrin formulation of the neurokinin‐1 receptor antagonist vestipitant

Article

Author: Muller, Fran ; Johnson, Brendan ; Hodsman, Peter ; Petit, Chantal ; Croy, Scott ; Brigandi, Richard A. ; Russ, Steven F.

AbstractVestipitant is a potent and selective neurokinin 1 (NK‐1) receptor antagonist that was investigated as a potential treatment for post‐operative nausea and vomiting (PONV). A previous mannitol‐based formulation of vestipitant was associated with hemolytic activity in preclinical studies. In an effort to reduce the hemolytic potential and develop an IV formulation of vestipitant that could be administered more rapidly, an IV formulation containing sulfobutylether‐7‐beta‐cyclodextrin (SBE7‐β‐CD, Captisol™) was developed and tested in a phase 1 clinical study. This was a randomized, single‐blind (subjects and investigator—blinded, sponsor‐unblinded), placebo controlled, dose escalation study in healthy subjects in which 7 cohorts of 8 subjects per cohort received SBE7‐β‐CD ‐based vestipitant (2 mg/mL) or placebo (saline) in a 3:1 ratio (active:placebo) at different doses and infusion rates. The results demonstrated the ability to infuse up to 48 mg vestipitant in a 2 mg/mL formulation over 30 seconds with no evidence of hemolytic effects. Cohorts of subjects at lower doses and longer infusion duration (>1 minute) reported more AEs related to the infusion site than those at the higher doses and faster infusion rates.

100 Deals associated with Vestipitant Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
D06293	Vestipitant Mesylate	-	DBSALT002111

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Postoperative Nausea and Vomiting	Phase 2	Belgium	GSK Plc	01 Dec 2004
Phobia, Social	Phase 2	Denmark	GSK Plc	01 Nov 2004
Phobia, Social	Phase 2	Norway	GSK Plc	01 Nov 2004
Phobia, Social	Phase 2	South Africa	GSK Plc	01 Nov 2004
Phobia, Social	Phase 2	Germany	GSK Plc	01 Nov 2004
Depressive Disorder, Major	Phase 2	-	GSK Plc	04 Nov 2002
Anxiety Disorders	Phase 2	-	GSK Plc	-
Anxiety Disorders	Phase 2	-	GSK Plc	-
Dyspepsia	Phase 2	-	GSK Plc	-
Nausea	Phase 2	-	GSK Plc	-