Delving into the Latest Updates on Dolasetron Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Anemet, Anzemet, Dolasetron

+ [7]

Target

5-HT3 receptor

Mechanism

5-HT3 receptor antagonists(Serotonin 3 (5-HT3) receptor antagonists)

Therapeutic Areas

Other Diseases

Active Indication

NauseaVomitingNausea and vomiting

Inactive Indication

Chemotherapy-induced nausea and vomitingPostoperative Nausea and VomitingPsychotic Disorders

Originator Organization

Sanofi

Active Organization

Liaoning Haisco Pharmaceutical Co., Ltd.

Sanofi

Inactive Organization

Hoechst Pakistan Ltd.

Validus Pharmaceuticals LLC

Drug Highest PhaseApproved

First Approval Date

US (11 Sep 1997),

Chemotherapy-induced nausea and vomitingPostoperative Nausea and Vomiting

Regulation-

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Structure

Molecular FormulaC20H26N2O7S

InChIKeyQTFFGPOXNNGTGZ-BHSFMSKKSA-N

CAS Registry878143-33-0

View All Structures (3)

The ICH E14/S7B Q&As highlighted the need for best practices concerning the design, execution, analysis, interpretation, and reporting of the in vivo non‐rodent QT assay as a component of the integrated risk assessment to potentially support a TQT waiver or substitute. We conducted a dog telemetry study to assess the effects on QTc of six reference compounds (five positive and one negative) previously evaluated by Darpo et al. (2015) in humans. The sensitivity of the assay to detect QTc increases was determined, and exposure–response analysis was performed, as done in clinical practice. By‐timepoint analysis showed QTc prolongation induced by moxifloxacin, dofetilide, dolasetron, ondansetron, and quinine within human relevant plasma exposures ranges. Moreover, a hysteresis was observed for quinine. As expected, levocetirizine showed no statistically significant effect on QTc across a range of exposure, well exceeding the therapeutic Cmax. Power analyses confirmed the study ability to detect statistically significant QTc changes of less than 10 milliseconds with 80% probability, even with a sample size as low as n = 4 animals. Finally, concentration‐QTc modeling enabled to predict the minimal plasma concentration needed to detect a 10 milliseconds QTc prolongation, including for quinine. The comparison with clinical available data supported the relevance of dogs under these experimental conditions as a robust translational predictor of drug‐induced QTc prolongation in humans as a key pillar of the integrated risk assessment.

01 Jun 2023·Minerva Anestesiologica

The efficacy of 5HT3-receptor antagonists in postoperative nausea and vomiting: the role of pharmacogenetics

Review

Author: Theodosopoulou, Polyxeni ; Staikou, Chryssoula ; Rekatsina, Martina

INTRODUCTIONGenetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The understanding of these mechanisms will help to identify the surgical patients who might benefit from specific prophylactic and therapeutic antiemetic treatment. The aim of the present review was to investigate gene polymorphisms that influence 5-hydroxytryptamine (serotonin) type 3 receptor antagonists (5HT3RA) efficacy in PONV.EVIDENCE AQUISITIONWe included articles published from 2005 to 2022, utilizing the electronic databases PUBMED, EMBASE, COHRANE Library and ScienceDirect. To explore the relationship between genetic variations and 5HT3 receptor antagonist efficacy in PONV we focused on three different gene polymorphisms: the cytochrome P450 mono-oxygenase system gene (CYP2D6), the adenosine triphosphate (ATP)-binding cassette subfamily B gene (ABCB1) as well as the 5HT3 receptor gene (5HT3R). We also explored the relationship between the above genetic variations and their impact on 5HT3RA efficacy in the context of chemotherapy induced nausea and vomiting.EVIDENCE SYNTHESISOur search retrieved a total of 70 articles; 29 of them were included in the present review. Regarding polymorphisms of the CYP2D6 gene and the efficacy of serotonin antagonists in PONV, the ultra-rapid metabolizer genotype was associated with reduced efficacy of ondansetron, dolasetron and tropisetron, with the latter presenting more pronounced failure in these patients, while granisetron's efficacy remained unaffected. Regarding variations in the ABCB1 gene, three polymorphisms ("2677G>T/A" in exon 21; "3435C>T" in exon 27; "C1236T" in exon 12) were associated with a better response to ondansetron and ramosetron, while they did not affect palonosetron's efficacy. Additionally, polymporphisms of the 5-HT3B receptor gene were associated with ondancetron's postoperative efficacy; the "100_-102AAG" deletion variant was associated with reduced efficacy, while the Y129S variant did not show any effect on the drug's antiemetic effect.CONCLUSIONSThis review highlights that inefficacy of a specific drug in managing PONV could be attributed to specific genetic profiles and patients would possibly benefit from a drug switch.

01 Jun 2022·Journal of International Medical Research

Incidence and risk factors of postoperative nausea and vomiting in lung cancer patients following lobectomy and application of analgesic pumps

Article

Author: Wu, Suwen ; Duan, Hao ; Lin, Peng ; Liao, Yixia ; Hong, Yutong ; Ma, Fen ; Gan, Chune ; Xu, Ye ; Jiang, Dongping ; Huang, Xiaoling

Objective To investigate the occurrence rate and risk factors of postoperative nausea and vomiting (PONV) in lung cancer patients following lobectomy and application of analgesic pumps. Methods This retrospective study reviewed clinical data from patients that had undergone lobectomy for lung cancer under general anaesthesia. The risk factors of PONV were analysed using binary logistic regression models. Results A total of 203 patients (97 females) were enrolled. The rate of PONV was 29.6% (60 of 203 patients) for all patients, 42.3% (41 of 97 patients) for female patients and 17.9% (19 of 106 patients) for male patients. Female patients undergoing thoracotomy (odds ratio [OR] 7.770, 95% confidence interval [CI] 1.747, 34.568) or having surgery durations ≥120 min (OR 4.493, 95% CI 1.502, 12.851) were significantly more susceptible to PONV. The risk of PONV in female patients that received postoperative dolasetron (100 mg, once a day) was significantly lower (OR 0.075, 95% CI 0.007, 0.834). For male patients, the risk of PONV was significantly lower in those with a body mass index ≥24 kg/m2 (OR 0.166; 95% CI 0.035, 0.782). Conclusion Female and male patients have different risk factors for PONV following lobectomy for lung cancer and application of analgesic pumps.

100 Deals associated with Dolasetron Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Dolasetron Mesylate	A04AA04	DB00757

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Nausea	CN	Liaoning Haisco Pharmaceutical Co., Ltd.	18 Jul 2011
Vomiting	CN	Liaoning Haisco Pharmaceutical Co., Ltd.	18 Jul 2011
Nausea and vomiting	CA	Sanofi	25 Sep 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Psychotic Disorders	Preclinical	EU	Hoechst Pakistan Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2004	Phase 3	Chemotherapy-induced nausea and vomiting	754	Palonosetron (PALO)	(tsaegvovgg) = xwtmdwionb bmvranccqw (wdfbcazgpi ) View more	-	15 Jul 2004
				Ondanestron/Dolasetron (OND/DOL)	(tsaegvovgg) = pvlfuaafun bmvranccqw (wdfbcazgpi ) View more