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International Journal of Medical... 2023Patients with myocardial infarction (MI) in intensive care units (ICU) are at high risk of death. Whether treatment with ondansetron (OND) at an early stage plays a...
Patients with myocardial infarction (MI) in intensive care units (ICU) are at high risk of death. Whether treatment with ondansetron (OND) at an early stage plays a protective role in critically ill patients with MI and its underlying mechanism remains unclear. A total of 4486 patients with MI were enrolled in the study cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into OND-medication groups or not. Propensity score matching (PSM) and regression analysis were performed to investigate the effect of OND on patients, accompanied by sensitivity analysis to evaluate the robustness of the results. Integrated with causal mediation analysis (CMA), we investigated the potential causal pathway mediated by the palate-to-lymphocyte ratio (PLR) between early OND treatment and clinical outcomes. Among patients with MI, 976 of them were treated with OND at the early stage while 3510 patients were not. The all-cause in-hospital mortality rate was significantly lower in the OND-medication group (5.6% vs 7.7%), accompanied by lower 28-day mortality (7.8% vs 11.3%) and 90-day mortality (9.2% vs 13.1%) rates. PSM analysis further confirmed the results for in-hospital mortality (5.7% vs 8.0%), 28-day mortality (7.8% vs 10.8%), and 90-day mortality (9.2% vs 12.5%). After adjusting for confounders, multivariate logistic regression analysis revealed that OND was associated with decreased in-hospital mortality (OR = 0.67, 95% CI: 0.49-0.91), and Cox regression confirmed the results for 28-day mortality and 90-day mortality with HR = 0.71 and 0.73, respectively. Most importantly, CMA demonstrated that the protective effect of OND on patients with MI was mediated by its anti-inflammatory effect through the regulation of PLR. Early use of OND in critically ill patients with MI may exert protective effects by reducing in-hospital mortality and 28- and 90-day mortality. The beneficial effects of OND on these patients were exerted through anti-inflammatory effects, at least in part.
Topics: Humans; Ondansetron; Critical Illness; Myocardial Infarction; Intensive Care Units; Critical Care; Retrospective Studies
PubMed: 37213673
DOI: 10.7150/ijms.81797 -
The Journal of International Medical... 2011This randomized, double-blind study evaluated the relative efficacy of palonosetron (a new, selective 5-hydroxytryptamine type 3 [5-HT(3)] receptor antagonist) and... (Comparative Study)
Comparative Study Randomized Controlled Trial
This randomized, double-blind study evaluated the relative efficacy of palonosetron (a new, selective 5-hydroxytryptamine type 3 [5-HT(3)] receptor antagonist) and ondansetron in preventing postoperative nausea and vomiting (PONV) in patients undergoing gynaecological laparoscopic surgery. Patients received either palonosetron 0.075 mg (n = 45) or ondansetron 8 mg (n = 45), intravenously, immediately before induction of general anaesthesia. The occurrence of nausea and vomiting and the severity of nausea according to a visual analogue scale were monitored immediately after the end of surgery and during the following 24 h. The incidence of PONV was significantly lower in the palonosetron group compared with the ondansetron group (42.2% vs 66.7%, respectively). There were no significant statistical differences in the visual analogue scale for nausea. In conclusion, palonosetron 0.075 mg was more effective than ondansetron 8 mg in preventing PONV.
Topics: Adult; Anesthesia; Antiemetics; Demography; Double-Blind Method; Female; Gynecologic Surgical Procedures; Humans; Incidence; Injections, Intravenous; Isoquinolines; Laparoscopy; Ondansetron; Palonosetron; Patient Satisfaction; Postoperative Nausea and Vomiting; Quinuclidines; Treatment Outcome
PubMed: 21672343
DOI: 10.1177/147323001103900207 -
Alcoholism, Clinical and Experimental... Oct 2022In a previous study, ondansetron, a serotonin 5-HT receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a previous study, ondansetron, a serotonin 5-HT receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants with moderate-to-severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5-HT (HTR3A), and 5-HT (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron-treated individuals with population-specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B.
METHODS
In this 16-week, double-blind, placebo-controlled, parallel-group clinical trial, adults with AUD were randomized to receive low-dose oral ondansetron (0.33 mg twice daily) or placebo stratified by "responsive" versus "nonresponsive" genotype defined using population-specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent-to-treat analysis were used to compare the treatment groups on the primary outcome-DPDD-and two secondary outcomes-heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment.
RESULTS
Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent-to-treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study-related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems.
CONCLUSIONS
We found no evidence that low-dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions.
Topics: Adult; Humans; Ondansetron; Alcoholism; Serotonin Plasma Membrane Transport Proteins; Serotonin; Pharmacogenomic Testing; Prospective Studies; Double-Blind Method; Treatment Outcome
PubMed: 36055978
DOI: 10.1111/acer.14932 -
PloS One 2014Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well...
Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.
Topics: Animals; Anticonvulsants; Hippocampus; Male; Mice, Inbred ICR; Ondansetron; Pentylenetetrazole; Piperidines; Proto-Oncogene Proteins c-fos; Seizures; Survival Analysis; gamma-Aminobutyric Acid
PubMed: 24690630
DOI: 10.1371/journal.pone.0093158 -
BioMed Research International 2022Ondansetron tablets that are directly compressed using crospovidone and croscarmellose as a synthetic super disintegrant are the subject of this investigation. A central...
Ondansetron tablets that are directly compressed using crospovidone and croscarmellose as a synthetic super disintegrant are the subject of this investigation. A central composite, response surface, randomly quadratic, nonblock (version 13.0.9.0) 3 factorial design is used to optimize the formulation (two-factor three-level). To make things even more complicated, nine different formulation batches (designated as F1-F9) were created. There were three levels of crospovidone and croscarmellose (+1, 0, -1). In addition to that, pre- and postcompressional parameters were evaluated, and all evaluated parameters were found to be within acceptable range. Among all postcompressional parameter dispersion and disintegration time, drug release experiments (to quantify the amount of medication released from the tablet) and their percentage prediction error were shown to have a significant influence on three dependent variables. Various pre- and postcompression characteristics of each active component were tested . Bulk density, tap density, angle of repose, Carr's index, and the Hausner ratio were all included in this analysis, as were many others. This tablet's hardness and friability were also assessed along with its dimension and weight variations. Additional stability studies may be conducted using the best batch of the product. For this study, we utilised the Design-Expert software to select the formulation F6, which had dispersion times of 17.67 ± 0.03 seconds, disintegration times of 120.12 ± 0.55 seconds, and percentage drug release measurements of 99.25 ± 0.36 within 30 minutes. Predicted values and experimental data had a strong correlation. Fast dissolving pills of ondansetron hydrochloride may be created by compressing the tablets directly.
Topics: Excipients; Ondansetron; Povidone; Solubility; Tablets
PubMed: 36046453
DOI: 10.1155/2022/2467574 -
Yonsei Medical Journal Jan 2010We compared the prophylactic effects of intravenously administered azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting (PONV) in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We compared the prophylactic effects of intravenously administered azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopic surgery under general anesthesia.
MATERIALS AND METHODS
We studied 98 ASA physical status I or II 20-65 years old, female patients, in this prospective, randomized, double blind study. Patients were randomly divided into two groups and received ondansetron 8 mg (group O) or azasetron 10 mg (group A) 5 min before the end of surgery. The incidence of PONV, Visual Analogue Scale (VAS) for pain, need for rescue antiemetic and analgesics, and adverse effects were checked at 1, 6, 12, 24, and 48 h postoperatively.
RESULTS
The overall incidence of PONV was 65% in group O and 49% in group A. The incidence of PONV was significantly higher in group O than in group A at 12-24 h postoperatively (nausea; 24% vs. 45%, p = 0.035, vomiting; 2% vs. 18%, p = 0.008), but there were no significant differences at 0-1, 1-6, 6-12 or 24-48 h.
CONCLUSION
In conclusion, azasetron (10 mg) produced same incidence of PONV as ondansetron (8 mg) in patients undergoing general anesthesia for gynecological laparoscopic surgery. Azasetron was more effective, in the intermediate post-operative period, between 12 and 24 h.
Topics: Adult; Aged; Bridged Bicyclo Compounds, Heterocyclic; Female; Gynecologic Surgical Procedures; Humans; Middle Aged; Ondansetron; Oxazines; Postoperative Nausea and Vomiting; Serotonin Antagonists; Treatment Outcome; Young Adult
PubMed: 20046519
DOI: 10.3349/ymj.2010.51.1.88 -
International Journal of Epidemiology Apr 2020Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy.
BACKGROUND
Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy.
METHODS
We evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate.
RESULTS
A total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4-1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0-2.9] to 2.1 (95% CI 1.1-4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0-9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects.
CONCLUSIONS
First trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.
Topics: Female; Heart Septal Defects, Ventricular; Humans; Infant, Newborn; Ondansetron; Pregnancy; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Risk Assessment
PubMed: 31860078
DOI: 10.1093/ije/dyz255 -
The British Journal of General Practice... Oct 2021
Topics: Acute Disease; Child; Gastroenteritis; Humans; Ondansetron; Primary Health Care; Vomiting
PubMed: 34593389
DOI: 10.3399/bjgp21X717089 -
Journal of Veterinary Pharmacology and... Aug 2014Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in...
Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.
Topics: Administration, Oral; Animals; Antiemetics; Area Under Curve; Biological Availability; Cats; Half-Life; Injections, Intravenous; Injections, Subcutaneous; Ondansetron
PubMed: 24330064
DOI: 10.1111/jvp.12094 -
Anesthesiology Aug 2008Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has never been confirmed and compared with both drugs under controlled conditions. The objective was to study the effects of droperidol and ondansetron alone or in combination on QT interval duration in healthy subjects.
METHODS
Sixteen healthy volunteers, eight males and eight females, were enrolled in this prospective, double-blind, randomized, placebo-controlled study. Subjects received 1 mg droperidol, 4 mg ondansetron, 1 mg droperidol plus 4 mg ondansetron, or a placebo, intravenously in a crossover design. Fridericia-corrected QT interval (QTcF) and plasma concentrations were measured repeatedly during 10 h at each study period. The primary endpoint was the maximal placebo time-matched and baseline-subtracted QTcF prolongation (DeltaDeltaQTcF).
RESULTS
Compared with placebo, both droperidol and ondansetron significantly prolonged the QTcF interval. DeltaDeltaQTcF prolongation was 25 +/- 8 ms after droperidol, significantly greater than the 17 +/- 10-ms prolongation with ondansetron (P = 0.014). The combination of droperidol and ondansetron significantly increased the mean maximal DeltaDeltaQTcF by 28 +/- 10 ms. The combination induced greater QTcF prolongation compared with ondansetron alone (P = 0.001), but not with droperidol alone (P = 0.33). There was no significant pharmacokinetic interaction between droperidol and ondansetron.
CONCLUSIONS
Under controlled conditions, both droperidol and ondansetron either alone or in combination induced significant marked QTc interval prolongation. However, the combination of both drugs did not significantly increase QTc prolongation compared with that induced by droperidol alone.
Topics: Adult; Antiemetics; Area Under Curve; Cross-Over Studies; Double-Blind Method; Droperidol; Drug Interactions; Electrocardiography; Female; Half-Life; Heart Rate; Humans; Linear Models; Long QT Syndrome; Male; Metabolic Clearance Rate; Ondansetron
PubMed: 18648229
DOI: 10.1097/ALN.0b013e31817fd8c8