Disease relevance of Zofran

• Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P less than 0.001) [1].
• Ondansetron for pruritus due to cholestasis [2].
• Improvement of cholestatic pruritus by ondansetron [3].
• Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial [4].
• Ondansetron and hyperemesis gravidarum [5].

Psychiatry related information on Zofran

• METHODS: Interdigestive motor activity was recorded manometrically in 16 subjects before and after administration of ondansetron, a selective 5-HT3 receptor antagonist [6].
• Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron [7].
• Ondansetron was found to augment certain stimulant, sedative, and discriminant effects of alcohol, without affecting psychomotor performance or alcohol pharmacokinetics [8].
• These data suggest that the reductions in alcohol consumption observed in animals and humans treated with ondansetron may be mediated by increases in subjective intoxication, and/or increases in the aversive effects of alcohol [8].
• Ondansetron treatment in Tourette's disorder: a 3-week, randomized, double-blind, placebo-controlled study [9].

High impact information on Zofran

• In a randomized, double-blind, crossover trial, we compared oral treatment with ondansetron (8 mg twice a day) and the dopamine D2 antagonist metopimazine (30 mg four times a day) with treatment with ondansetron alone for three days in 30 patients who had vomited during the previous cycle of chemotherapy [10].
• We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells, and that ondansetron acts by blocking S3 receptors for serotonin [11].
• Pancreatitis associated with ondansetron [12].
• The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea [13].
• Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission [4].

Chemical compound and disease context of Zofran

• Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group [14].
• The rate of complete control of emesis was 61.2% in the granisetron group and 67.1% in the ondansetron group (95% CI, -11.7 to -0.1) [15].
• Is oral ondansetron really efficacious in the control of cisplatin-induced delayed emesis [16]?
• CONCLUSION: Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis [17].
• Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia [18].

Biological context of Zofran

• No relationships were apparent between peak ondansetron concentration (Cmax) or area under the concentration versus time curve (AUC) and number of emetic episodes [19].
• This study examined the effects of ondansetron, a highly selective 5-HT3 antagonist, on the P50 auditory evoked potential [20].
• CONCLUSIONS: These data indicate that the pharmacokinetics of ondansetron in children from 3 to 12 years old are predictable and similar to those in adults [21].
• The bioavailability of oral ondansetron was reduced from 60% to 40% (P < .01) by rifampin [22].
• CONCLUSIONS: This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy [23].

Anatomical context of Zofran

• The following inhibition was fully antagonized by ketotifen (mast cell stabilizer), granisetron and ondansetron (5-HT3 antagonists), RP-67,580 (NK1 antagonist), and perivagal capsaicin pretreatment [24].
• METHODS: The effects of ondansetron and placebo on fasting and postprandial colonic tone and motility in 10 patients with carcinoid diarrhea were compared using a manometry-barostat assembly positioned in the upper descending colon [25].
• METHODS: Twenty patients who received 4 days of TBI as part of their preparative regimen before bone marrow transplantation were randomized to receive either 8-mg oral doses of ondansetron or placebo [19].
• The effects of ondansetron, a potent and selective antagonist of the 5-HT3 receptor, were examined on (1) frequency of the hippocampal theta rhythm, (2) induction of LTP in field CA1 of freely moving rats, and (3) retention of olfactory and spatial memory in tasks known to depend on an intact hippocampus [26].
• The pA2 of some selected compounds against the 5-HT3 agonist 2-methyl-5HT in the guinea pig ileum was in the range of tropisetron or ondansetron, and one of them, 7e, was more potent than these reference compounds by approximately 2 or 3 orders of magnitude [27].

Associations of Zofran with other chemical compounds

• The results suggest that the suppression of gastric activity fronts is achieved via the suppression of plasma motilin peaks because in the presence of ondansetron a motilin agonist like erythromycin restores the gastric phase 3 [6].
• CONCLUSION: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy [14].
• PATIENTS AND METHODS: Cancer patients (n = 609) receiving first-course cisplatin chemotherapy were randomized to one of three treatments: 1.8 or 2.4 mg/kg dolasetron mesylate salt (equivalent to 1.3 and 1.8 mg/kg dolasetron base, respectively) or 32 mg ondansetron [28].
• This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated [17].
• CONCLUSION: Metopimazine plus ondansetron was significantly superior to ondansetron alone, concerning all efficacy parameters assessed, in patients who received platinum-based chemotherapy [29].

Gene context of Zofran

• Ondansetron chronic effect on CCK-4-induced behavioral changes needs further exploration [30].
• Docking of 5-HT3 antagonists granisetron, tropisetron, ondansetron, dolasetron ('setrons), and (+)-tubocurarine suggests an aromatic binding cleft behind a hydrophilic vestibule [31].
• To determine if this pathway plays a role in the pathophysiology of inflammation, we investigated the effects of spinally administered ondansetron (a selective 5HT3 receptor antagonist) on deep dorsal horn neuronal responses in carrageenan inflamed and naïve animals using in vivo electrophysiology [32].
• We offer several alternative explanations for this event, all of which rest on disruption of serotonergic and/or dopaminergic transmission and which could also involve inhibition by paroxetine of the P450 enzyme, CYP2D6, which metabolizes ondansetron [33].
• To summarize, this study has identified the involvement of CYP2D6 in the formation of the hydroxylated metabolites of tropisetron and ondansetron and in addition of CYP3A in ondansetron hydroxylation [34].

Analytical, diagnostic and therapeutic context of Zofran

• Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024) [1].
• Ondansetron for patients given abdominal radiotherapy [35].
• The incidence of gastric activity fronts before and after ondansetron was compared with a control group that had not received ondansetron [6].
• The comparative clinical trials show that a single intravenous (i.v.) dose of granisetron 3 mg is as effective as multiple (8 mg x 3) or single (32 mg) i.v. doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin [36].
• PURPOSE: To evaluate oral ondansetron in the prevention of total-body irradiation (TBI)-induced nausea and vomiting [19].

References