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  1. Keat CH, Ghani NA
    Asian Pac J Cancer Prev, 2013;14(12):7701-6.
    PMID: 24460356
    BACKGROUND: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective.

    MATERIALS AND METHODS: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness.

    RESULTS: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen.

    CONCLUSIONS: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

    Matched MeSH terms: Granisetron/therapeutic use*
  2. Keat CH, Phua G, Abdul Kassim MS, Poh WK, Sriraman M
    Asian Pac J Cancer Prev, 2013;14(1):469-73.
    PMID: 23534775
    BACKGROUND: The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) among patients receiving low emetogenic chemotherapy (LEC) with and without granisetron injection as the primary prophylaxis in addition to dexamethasone and metochlopramide.

    MATERIALS AND METHODS: This was a single-centre, prospective cohort study. A total of 96 patients receiving LEC (52 with and 42 without granisetron) were randomly selected from the full patient list generated using the e-Hospital Information System (e-His). The rates of complete control (no CINV from days 1 to 5) and complete response (no nausea or vomiting in both acute and delayed phases) were identified through patient diaries which were adapted from the MASCC Antiemesis Tool (MAT). Selected covariates including gender, age, active alcohol consumption, morning sickness and previous chemotherapy history were controlled using the multiple logistic regression analyses.

    RESULTS: Both groups showed significant difference with LEC regimens (p<0.001). No differences were found in age, gender, ethnic group and other baseline characteristics. The granisetron group indicated a higher complete response rate in acute emesis (adjusted OR: 0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups showed similar complete control and complete response rates for acute nausea, delayed nausea and delayed emesis.

    CONCLUSIONS: Granisetron injection used as the primary prophylaxis in LEC demonstrated limited roles in CINV control. Optimization of the guideline-recommended antiemetic regimens may serve as a less costly alternative to protect patients from uncontrolled acute emesis.

    Matched MeSH terms: Granisetron/therapeutic use*
  3. Zulkifli MH, Viswenaden P, Jasamai M, Azmi N, Yaakob NS
    Biomed Pharmacother, 2019 Feb 20;112:108630.
    PMID: 30797147 DOI: 10.1016/j.biopha.2019.108630
    5-HT3R antagonists such as ondansetron, granisetron and tropisetron have been clinically used to treat nausea and vomiting in chemotherapy patients. However, current study and research revealed novel potentials of these ligands in other diseases like inflammation, Alzheimer's, and drug abuse. Towards utilising these drugs as anti-smoking agents to treat nicotine dependence problem, there are conflicting reports regarding the potential of these ligands in modulating the effects of nicotine in both human and animal behavioural studies. This is complicated by the heterogeneity of 5-HT3R itself, cross regulation between nicotinic acetylcholinergic receptor (nAChR) and distinct pharmacological profiles of 5-HT3R antagonists. This review gathered existing studies conducted investigating the potential of "-setron" class of 5-HT3R antagonists in modulating nicotine effects. We proposed that the mechanism where 5-HT3R antagonists mediate the effects of nicotine could be attributed by both direct at 5-HT3R and indirect mechanism in nicotine addiction downstream regulation. The indirect mechanism mediated by the 5-HT3R antagonist could be through α7 nAChR, 5-HT1B receptor (5-HT1BR), 5-HT1C receptor (5-HT1CR), calcineurin activity, p38 MAPK level, PPAR-γ and NF-κβ. Our review suggested that future studies should focus on newer 5-HT3R antagonist with superior pharmacological profile or the one with multitarget action rather than high selectivity at single receptor.
    Matched MeSH terms: Granisetron
  4. 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: Granisetron/therapeutic use*
  5. Martins J, Brijesh S
    J Ethnopharmacol, 2019 Oct 07.
    PMID: 31600560 DOI: 10.1016/j.jep.2019.112280
    ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina variegata, commonly referred to as 'tiger's claw' or 'Indian coral tree' and 'Parijata' in Sanskrit, belongs to the Fabaceae family. It is a plant native to the coast of India, China, Malaysia, East Africa, Northern Australia and distributed in tropical and subtropical regions worldwide. In traditional medicine, 'Paribhadra' an Indian preparation, makes use of the leaves and bark of E. variegata to destroy pathogenic parasites and relieve joint pains. E. variegata is known to exhibit anxiolytic and anti-convulsant activities. Folkore medicine also suggests that E. variegata barks act on the central nervous system. However, there is a lack of data demonstrating this. The anti-depressant activity of E. variegata bark has not been reported in literature.

    AIM OF THE STUDY: Our study focuses on previously unreported anti-depressant activity of E. variegata bark ethanolic extract (EBE) and determination of its mechanism of action possibly through regulation of monoamine oxidase activity in mouse brain homogenates.

    MATERIALS AND METHODS: EBE was characterized using standard protocols for phytochemical analysis, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analysis. Anti-depressant activity of EBE (50, 100, 200 and 500 mg/kg) was evaluated in Swiss white albino mice using acute and chronic forced swim test (FST) models. Furthermore, the potential use of the extract as an adjunct to selective serotonin reuptake inhibitor (SSRI), escitalopram, was evaluated using the chronic unpredictable mild stress test model wherein inhibitory effects on monoamine oxidase (MAO) A and B were assessed by spectrophotometric-chemical analysis in mouse whole brain homogenates.

    RESULTS: The extract showed significant reduction in immobility time periods in both acute (200 mg/kg) and chronic (100, 200 and 500 mg/kg) FST models. When used as an adjunct with escitalopram (15 mg/kg), the extract (100, 200 and 500 mg/kg) showed significantly greater inhibition of MAO-A and B activities when compared to escitalopram alone (30 mg/kg). Phytochemical analysis of EBE revealed presence of sugars, steroids, glycosides, alkaloids and tannins. LC-MS and GC-MS analysis identified components such as 2-amino-3-methyl-1-butanol, phenylethylamine, eriodictyol, daidzein and pomiferin, N-ethyl arachidonoyl amine, inosine diphosphate, trimipramine, granisetron, 3,4-dihydroxymandelic acid, ethyl ester, tri-TMS and dodecane, previously reported for their anti-depressant activity.

    CONCLUSIONS: The study thus demonstrated potential for use of the E. variegata bark ethanolic extract as an adjunct to currently available SSRI treatment. The study also identified components present in E. variegata bark ethanolic extract that may be responsible for its anti-depressant activity. Furthermore, the study thus confirms the traditional use of E. variegata barks in improving CNS function through its anti-depressant like activity.

    Matched MeSH terms: Granisetron
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