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Formulation and in vivo evaluation of ondansetron orally disintegrating tablets using different superdisintegrants

Sheshala R, Khan N, Chitneni M, Darwis Y

Arch Pharm Res, 2011 Nov;34(11):1945-56.
PMID: 22139694 DOI: 10.1007/s12272-011-1115-y

The aim of this study was to formulate cost effective taste-masked orally disintegrating tablets of ondansetron, a bitter drug using different superdisintegrants by a wet granulation technique. Microcrystalline cellulose (Avicel) as a diluent and disintegrant in addition to aspartame as a sweetener were used in all formulations. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. The tablets' hardness was maintained in the range of 2-3 kg and friability was <1% for all batches. All tablet formulations disintegrated rapidly in vitro within 5.83 to 33.0 sec. The optimized formulation containing 15% Polyplasdone XL-10 released more than 90% of drug within 5 min and the release was comparable to that of a commercial product. In human volunteers, optimized formulation was found to have a pleasant taste and mouth feel and they disintegrated in the oral cavity within 12 sec. The stability results were also satisfactory. A pharmacokinetic study with the optimized formulation was performed in comparison with a reference (Zofer MD 8®) and they were found to be bioequivalent. In conclusion, a cost effective ondansetron orally disintegrating tablet was successfully prepared with acceptable hardness, desirable taste and rapid disintegration in the oral cavity.

Matched MeSH terms: Serotonin 5-HT3 Receptor Antagonists/analysis; Serotonin 5-HT3 Receptor Antagonists/pharmacokinetics*; Serotonin 5-HT3 Receptor Antagonists/pharmacology; Serotonin 5-HT3 Receptor Antagonists/chemistry*
Potential Roles of 5-HT3 Receptor Antagonists in Reducing Chemotherapy-induced Peripheral Neuropathy (CIPN)

Satiamurthy R, Yaakob NS, Shah NM, Azmi N, Omar MS

Curr Mol Med, 2023;23(4):341-349.
PMID: 35549869 DOI: 10.2174/1566524022666220512122525

5-HT3 receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT3 receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5- HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT3 receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.

Matched MeSH terms: Serotonin 5-HT3 Receptor Antagonists/adverse effects
Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: a multinational study

Chanthawong S, Lim YH, Subongkot S, Chan A, Andalusia R, Ahmad Bustamam RS, et al.

Support Care Cancer, 2019 Mar;27(3):1109-1119.
PMID: 30112718 DOI: 10.1007/s00520-018-4400-1

PURPOSE: Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries.
METHODS: Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed.
RESULTS: Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries.
CONCLUSION: The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Matched MeSH terms: Serotonin 5-HT3 Receptor Antagonists/economics; Serotonin 5-HT3 Receptor Antagonists/therapeutic use
Genetic polymorphisms in the three malaysian races effect granisetron clinical antiemetic actions in breast cancer patients receiving chemotherapy

Hassan BA, Yusoff ZB

Asian Pac J Cancer Prev, 2011;12(1):185-91.
PMID: 21517255

INTRODUCTION: Nausea and vomiting are recognized as two separate and distinct conditions with a wide spectrum of etiologies either directly associated with cancer itself or its treatment. According to the new ranking of chemotherapy side effects, nausea is the number one or the most disturbing side effects while vomiting is the third and sometimes the fifth. The introduction of 5-HT3-recptor antagonists in the early of 1990s has revolutionized the treatment of nausea and vomiting, these agents remaining the mainstay of antiemetic therapy today. Ethnic variation (due to genetic polymorphisms) may lead to diversity in antiemetic treatment pharmacokinetic and pharmacodynamic properties, in terms of distribution, elimination, disposition and clinical effects. The aim of the present study was to clarify genetic polymorphism effects in the three main races in Malaysia i.e., Malay, Chinese and Indian, on the clinical antiemetic effects of granisetron.

METHODS: In this longitudinal prospective observational study, 158 breast cancer patients treated with chemotherapy were monitored for nausea and vomiting in the first 24 hours after chemotherapy administration. The patients were then followed up again after 3 to 5 days of chemotherapy.

RESULTS: Genetic polymorphisms in the three races in Malaysia have significant effect on granisetron clinical antiemetic action because each is characterized by variant CYP3A4 enzymatic action.

CONCLUSION: According to the result, different type of 5-HT3 receptor antagonists, such as tropisetron and dolasetron which are predominantly metabolized by CYP2D6, should be used especially for Chinese breast cancer patients.

Study site: Hospital Pulau Pinang

Matched MeSH terms: Serotonin 5-HT3 Receptor Antagonists/therapeutic use
Novel 5-HT3 receptor antagonist QCM-4 attenuates depressive-like phenotype associated with obesity in high-fat-diet-fed mice

Kurhe Y, Mahesh R, Devadoss T

Psychopharmacology (Berl), 2017 Apr;234(7):1165-1179.
PMID: 28238069 DOI: 10.1007/s00213-017-4558-0

RATIONALE: Depression associated with obesity remains an interesting area to study the biological mechanisms and novel therapeutic intervention.
OBJECTIVES: The present study investigates the effect of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers of depression associated with obesity such as plasma insulin resistance, hippocampal cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic factor (BDNF), serotonin (5-HT) concentrations, hippocampal neuronal damage, and p53 protein expression in high-fat-diet (HFD)-fed mice.
METHODS: Obesity was experimentally induced in mice by feeding with HFD for 14 weeks followed by administration of QCM-4 (1 and 2 mg/kg, p.o.)/standard escitalopram (ESC) (10 mg/kg, p.o.)/vehicle (10 ml/kg, p.o.) for 28 days. Behavioral assays such as sucrose preference test (SPT); forced swim test (FST); elevated plus maze (EPM); biochemical assays including oral glucose tolerance tests (OGTT), insulin, cAMP, BDNF, and 5-HT concentrations; and molecular assays mainly histology and immunohistochemistry (IHC) of p53 protein in the dentate gyrus (DG), CA1, and CA3 regions of hippocampus in HFD fed mice were performed.
RESULTS: Chronic treatment with QCM-4 in HFD-fed mice reversed the behavioral alterations in SPT, FST, and EPM. QCM-4 showed poor sensitivity for plasma glucose, improved insulin sensitivity, increased hippocampal cAMP, BDNF, and 5-HT concentrations. In the hippocampal DG, CA1, and CA3 regions, QCM-4 treatment improved the neuronal morphology in the histopathology and inhibited p53 protein expression in IHC assay in HFD-fed mice.
CONCLUSION: QCM-4 attenuated the depressive-like phenotype in HFD-fed mice by improving behavioral, biochemical, and molecular alterations through serotonergic neuromodulation.

Matched MeSH terms: Serotonin 5-HT3 Receptor Antagonists/therapeutic use*