Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new zofran research articles will be listed here shortly after becoming available to us.
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Parkinsonism Relat Disord. 1997 Dec; 3(4): 191-3
Arnold G, Schwarz J, Macher C, Oertel WH
Dopaminergic stimulation by apomorphine causes severe adverse effects such as vomiting and sedation. We compared the effectiveness of the serotonin 5-HT(3) antagonistic antiemetic drug ondansetron in a single oral dose with the standard regimen using domperidone TID 2 days prior to stimulation. In a double blind, randomised parallel group design, 16 previously untreated Parkinsonian patients were investigated, eight patients received domperidone (total dose 140 mg, starting 2 days prior to apomorphine challenge) and eight patients ondansetron (8 mg single dose 2 hr prior to investigation). Adverse events following the injection of 2-3 mg apomorphine were rated on a four-item scale. In an overall analysis, dopaminergic stimulation was significantly better tolerated, if the patients received domperidone, whereas more severe adverse effects were noted after ondansetron. Following ondansetron pre-treatment, seven patients experienced marked nausea or vomiting, all patients yawned, six patients had marked sedation, two patients a blood pressure decrease of more than 20 mmHg, and four patients strong sweating. In contrast, the latter side effect was found only in one patient pre-treated with domperidone, no patient had significant blood pressure decrease, all patients yawned, and seven domperidone patients had slight nausea. We conclude that oral ondansetron is no alternative to domperidone in the pre-treatment regimen of dopaminergic stimulation.
A Novel Approach to Optimize and Formulate Fast Disintegrating Tablets for Nausea and Vomiting.
AAPS PharmSciTech. 2008 Jun 27;
Goel H, Vora N, Rana V
The aim of this study was to optimize and formulate fast disintegrating tablets (FDTs) for nausea and vomiting using aminoacetic acid, carmellose and sodium alginate with enough mechanical strength. Ondansetron HCl (water soluble) or domperidone (water insoluble) drug were added to FDTs and their disintegration behaviour was evaluated. Plackett Burman Screening Design was used to screen the independent active process variables [concentration of aminoacetic acid (X (1)), concentration of carmellose (X (2)) and tablet crushing strength (X (3))] which were found to actively influence the dependent variables [disintegration time in the mouth (DT), wetting time (WT), and water absorption ratio (WAR)] for both the drugs. Also, the coefficients of active variables (DT, WT and WAR) of FDTs containing domperidone was found to be significantly different (P < 0.05) from the coefficients of active factors (X (1), X (2) and X (3)) containing ondansetron HCl FDTs. Further, FDTs containing domperidone was prepared according to central composite design for estimating the effect of active factors (X (1), X (2), X (3)) in extended spherical domain. The regression analysis of quadratic fit revealed that DT, WT and WAR were 98% correlated with active factors (X (1), X (2) or X (3)). The optimized domperidone FDTs were further compared with superdisintegrants (croscarmellose sodium or crospovidone). The data revealed that optimized domperidone FDTs were better than domperidone FDTs containing croscarmellose or crospovidone. Hence, this novel excipients combination can be used for delivery of water insoluble drugs in place of superdisintegrants.
Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder.
Neuropsychiatr Dis Treat. 2005 Sep; 1(3): 231-43
Aouizerate B, Guehl D, Cuny E, Rougier A, Burbaud P, Tignol J, Bioulac B
The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.
Chang Gung Med J. 2008 Mar-Apr; 31(2): 167-74
Chen PT, Liaw CC
BACKGROUND: This study examined whether different ondansetron dosing schedules plus dexamethasone influenced antiemetic efficacy during multiple cycles of cisplatin-based chemotherapy (CT). Antiemetic activities between previous CT and subsequent cycles were compared. METHODS: The cross-over study involved 424 patients. Arm A, three doses of 8 mg ondansetron given intravenously (IV) at 4-hourly intervals plus dexamethasone 20 mg IV at the start of CT, followed by dexamethasone 5 mg IV every 12 hours. Arm B, as arm A but the three doses of 8 mg ondansetron were given at 24-hourly intervals. For those with complete protection from emesis in both arms, a single dose of 8 mg ondansetron (arm C) was tried during the following CT. Once complete protection of emesis could not be maintained, arm A regimens were administered in the subsequent cycles of CT. RESULTS: There were 384, 377 and 147 patients in arm A, arm B and arm C, respectively. Complete control of acute and delayed nausea/vomiting obtained in arm A were 91.4%/94.8% and 59.6%/70.1%, and in arm B were 90.4%/92.3% and 61.3% 72.7%. There was no significant difference in antiemetic efficacy between both arms. Decreased incidence of and delayed onset of nausea on day 2 were observed in arm B (p = 0.002). The emetic severity during previous CT correlated significantly with those of the subsequent CT. The complete control of nausea/vomiting was maintained in 81.6%/72.1% of arm C patients during the following 3rd-6th cycles of CT. CONCLUSION: No difference in antiemetic efficacy was shown when a triple 8 mg dose of ondansetron was given at 4-hourly intervals or at 24-hourly intervals. However, the latter improved nausea on day 2. A single 8 mg dose of ondansetron can maintain antiemetic efficacy in the majority of complete responders in arm A and arm B.
Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats.
Am J Physiol Gastrointest Liver Physiol. 2008 Jun 19;
Taniguchi H, Ariga H, Zheng J, Ludwig K, Mantyh C, Pappas TN, Takahashi T
Endogenous ghrelin causes interdigestive contractions of the stomach in rats. In contrast, previous studies showed that 5-HT3 and 5-HT4 receptors were involved in regulating intestinal interdigestive contractions. We studied the possible role of endogenous ghrelin and 5-HT regulating interdigestive gastrointestinal (GI) contractions in rats. Four strain gauge transducers were implanted on the antrum, duodenum, and proximal and distal jejunum. After an overnight fast, GI contractions were recorded in freely moving conscious rats and ghrelin receptor antagonists [(D-lys3)GHRP6; 1 micromol/kg], 5-HT3 antagonists (Ondansetron; 0.5 mg/kg) and 5-HT4 antagonists (GR 125,487; 1 mg/kg) were administered (bolus, iv). To evaluate the relationship between the luminal concentrations of 5-HT and phase III-like contractions of the duodenum, duodenal juice was collected via the intraduodenal catheter. 5-HT content of the duodenal juice was measured by HPLC. (D-lys3)GHRP6 significantly attenuated the occurrence and amplitude of phase III-like contractions of the antrum, but not the duodenum and jejunum. 5-HT4 antagonists significantly reduced spontaneous phase III-like contractions of the jejunum, without affecting those of the antrum and duodenum. In contrast, 5-HT3 antagonists did not affect phase III-like contractions in GI tract. Luminal concentration of 5-HT at the phase III-like contraction (36.0 +/-13.3 ng/ml, n=9) was significantly higher than that at the phase I-like contractions of the duodenum (4.9 +/-1.6 ng/ml, n=9, P
Alcohol Clin Exp Res. 2008 Jun 19;
Roache JD, Wang Y, Ait-Daoud N, Johnson BA
Background: Previously, we reported that ondansetron was efficacious at treating early-onset (/=26-years old) alcoholics in a double-blind, randomized, placebo-controlled clinical trial (n = 321 enrolled patients, 271 of them randomized). Randomized participants underwent 11 weeks of treatment with ondansetron (1, 4, or 16 mug/kg twice daily; n = 67, 77, and 71, respectively) or identical placebo (n = 56), plus weekly standardized group cognitive behavioral therapy. Methods: For this study, we reanalyzed the original sample to determine whether the Type A/B typological classification predicts ondansetron treatment response. In this comparative analysis, k-means clustering was applied to 19 baseline measures of drinking behavior, psychopathology, and social functioning, similar to those used by Babor in the original typological derivation. A 2-factor solution described robustly 2 groups phenomenologically consistent with Type A/B classification. Subjects were subdivided into early- and late-onset alcoholics. Results: Seventy-two percent of Type B subjects had early-onset alcoholism (EOA); 67% of Type A subjects had late-onset alcoholism (LOA). The A/B typology better discriminated 2 clusters based upon baseline severity of alcoholism. There was a significant effect (p < 0.05) for Type B alcoholics to respond to ondansetron (4 mug/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early-onset vs. late-onset classification predicted ondansetron response substantially better than Type A/B classification, which did not add to the prediction of treatment outcome. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with EOA but ineffective in the 28% of Type B alcoholics with LOA. Conclusions: Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early- vs. late-onset classification is, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism.
Tumori. 2008 Mar-Apr; 94(2): suppl 26-32
Pradelli L, Eandi M
Tumori. 2008 Mar-Apr; 94(2): suppl 14-22
Di Maio M, Gallo C, Perrone F
[Pharmacokinetic and pharmacodynamic features of palonosetron]
Tumori. 2008 Mar-Apr; 94(2): suppl 6-13
Genazzani AA, Billington RA
Emergency department management of gastro-enteritis in Australia and New Zealand.
J Paediatr Child Health. 2008 Jun 18;
Schutz J, Babl FE, Sheriff N, Borland M,
Objective: Comparison of clinical practice guideline (CPG) recommendations and reported physician management of gastro-enteritis at Paediatric Research in Emergency Departments International Collaborative (PREDICT) network sites as a baseline for further randomised controlled trials. Methods: Two part survey comprising: (i) review of CPGs from PREDICT sites for gastro-enteritis; and (ii) survey of senior emergency department physicians regarding the management of gastro-enteritis. Results: All 11 PREDICT sites participated. Nine CPGs were available with three sites using a common CPG. For moderate dehydration, eight CPGs advocated nasogastric (NG) rehydration in preference to intravenous (IV) rehydration. The IV route was reserved for severe dehydration or failed NG rehydration. In the second component of the survey, 78 of 83 (94%) physicians responded. In moderate dehydration, 82% of respondents used NG rehydration. In severe dehydration, 86% used IV fluids; 12% used NG and 3% an initial IV bolus followed by NG fluid. Serum electrolytes were measured universally with IV fluid use and by 22% using NG rehydration. The IV fluid bolus was with normal saline (86%). Fifty-four per cent used anti-emetics 'rarely' or 'sometimes'. The commonest agents were ondansetron (60%) and metoclopramide (29%). Conclusions: CPG recommendations and physician practice for the management of gastro-enteritis were similar across PREDICT sites with a focus on NG for moderate dehydration and IV for severe dehydration. A variety of fluids and administration rates were used. Anti-emetics were used infrequently. The efficacy and safety of newer anti-emetics should be explored in collaborative studies. Collaborative development of new CPGs should be considered to simplify fluid regimens.