Showing papers on "Granisetron published in 2006"
TL;DR: Findings in humans confirmed that the mechanism of the analgesic action of acetaminophen is linked to the serotonergic system and that it is inhibited by tropisetron, a 5‐hydroxytryptamine type 3 antagonist.
Abstract: Objectives
Preclinical studies have suggested that the mechanism of the analgesic action of acetaminophen (INN, paracetamol) is linked to the serotonergic system and that it is inhibited by tropisetron, a 5-hydroxytryptamine type 3 antagonist. The aim of this study was to confirm these findings in humans.
Methods
Twenty-six rapid metabolizers of tropisetron were included in this double-blind crossover study. After ethical approval, at weekly intervals, the subjects took a single oral dose of 1 g acetaminophen combined with either intravenous tropisetron (5 mg), granisetron (3 mg), or placebo (saline solution). For each session, the analgesic effect of acetaminophen was assessed by use of a pain self-evaluation instrument, the Pain Matcher. The pain detection threshold was determined 5 times over the period of the 4 postdosing hours. The area under the curve (0–4 hours) (mean ± SD) of acetaminophen/tropisetron and the area under the curve of acetaminophen/granisetron were compared with the effect of acetaminophen/placebo. Blood samples for acetaminophen concentration measurements were taken to evaluate a pharmacokinetic interaction.
Results
The analgesic effect of acetaminophen/placebo (expressed as the area under the curve of the percentage of the individual pain score reported at baseline along time [% · min]) (2145 ± 2901 % · min) was totally inhibited by both tropisetron (89 ± 1747 % · min, P = .007) and granisetron (45 ± 2020 % · min, P = .002). Acetaminophen concentration was not significantly different when associated with tropisetron (P = .919) or granisetron (P = .309).
Conclusion
These results clearly show for the first time in humans that the coadministration of tropisetron or granisetron with acetaminophen completely blocks the analgesic effect of acetaminophen. They support the hypothesis that the mechanism of the analgesic action of acetaminophen might involve the serotonergic system. Furthermore, they demonstrate a pharmacodynamic interaction between these 2 types of drugs, which are frequently coadministered, especially in cancer patients.
Clinical Pharmacology & Therapeutics (2006) 79, 371–378; doi: 10.1016/j.clpt.2005.12.307
264 citations
TL;DR: Dexamethasone and the anti-serotinergic agents appear to be the most effective agents for the prophylaxis for POV in children undergoing tonsillectomy, with or without adenoidectomy.
Abstract: Postoperative vomiting (POV) remains one of the commonest causes of significant morbidity after tonsillectomy in children. A variety of prophylactic anti-emetic interventions have been reported, but there has only been a limited systematic review in this patient group. A systematic search was performed by using Cochrane Controlled Trials Register, MEDLINE and EMBASE to identify double-blind, randomized, placebo-controlled trials of prophylactic anti-emetic interventions in children undergoing tonsillectomy, with or without adenoidectomy. The outcome of interest was POV in the first 24 h. Summary estimates of the effect of each prophylactic anti-emetic strategy were derived using fixed effect meta-analysis. Where appropriate, dose–response effects were estimated using logistic regression and 22 articles were identified. Good evidence was found for the prophylactic anti-emetic effect of dexamethasone [odds ratio (OR) 0.23, 95% CI 0.16–0.33], and the serotinergic antagonists ondansetron (OR 0.36, 95% CI 0.29–0.46), granisetron (OR 0.11, 95% CI 0.06–0.19), tropisetron (OR 0.15, 95% CI 0.06–0.35) and dolasetron (OR 0.25, 95% CI 0.1–0.59). Metoclopramide was also found to be efficacious (OR 0.51, 95% CI 0.34–0.77). There is not sufficient evidence to suggest that dimenhydrinate, perphenazine or droperidol, in the doses studied, are efficacious, nor were gastric aspiration or acupuncture. In conclusion, dexamethasone and the anti-serotinergic agents appear to be the most effective agents for the prophylaxis for POV in children undergoing tonsillectomy.
136 citations
TL;DR: It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.
Abstract: We investigated the efficacy of granisetron and dolasetron in preventing postoperative nausea and vomiting. Because the metabolism of the various antiemetic 5-hydroxytryptamine type 3 (5-HT3) antagonists involves different isoforms of the hepatic cytochrome P450 system, we examined the relationship between the clinical efficacy of these drugs and polymorphic cytochrome P450 2D6 (CYP2D6) genotype. This prospective, randomized, double-blind study involved 150 adult patients with a moderate to high risk for postoperative nausea and vomiting. All subjects received dexamethasone at induction of anesthesia followed by either 12.5 mg of dolasetron or 1 mg of granisetron. We analyzed the number of complete responders (no vomiting or rescue medication) during the first 24 hours after surgery. CYP2D6 genotyping was performed using a TaqMan real-time polymerase chain reaction. A complete response was more frequent in the granisetron group (54.7%) compared with the dolasetron group (38.7%, P < 0.05). In subjects receiving dolasetron, carriers of the duplication of the CYP2D6 allele predicting ultrarapid metabolizer status had more frequent vomiting episodes (P < 0.05) than patients in the granisetron group. It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.
52 citations
TL;DR: Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway.
Abstract: Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT3 receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis. In 2003, a new 5-HT3 receptor antagonist, palonosetron HCL (Aloxi®), was introduced to the U.S. market. Palonosetron was found to be effective in preventing delayed CINV. Indeed, palonosetron was the first and only 5-HT3 receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of substance P in the emetic process led to the development of aprepitant (Emend®) for the prevention of delayed emesis in combination with 5-HT3 receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in emetic sensitivity and responsiveness to antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional therapies.
51 citations
TL;DR: A meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT3RA.
Abstract: Background:Antiemetic guidelines recommend a combination of serotonin (5-HT3) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid.Objective:To assess the safety profiles of 5-HT3 receptor antagonist (5-HT3RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV).Methods:A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966–September 2005) using the key terms 5-HT3, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT3RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT3RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with ...
37 citations
TL;DR: Evaluating the ECG changes after administration of 5‐HT3 receptor antagonists and chemotherapeutic agents in children with cancer finds no sufficient data in children who are treated with cytotoxic agents.
Abstract: Background
The antiemetic efficacy of serotonin-type 3 (5-HT3) receptor antagonists has been found to be superior to older antiemetic drugs in cancer patients. Following the administration of these agents, changes in ECG parameters and increased or decreased heart rates have been demonstrated, but there is no sufficient data in children with cancer who are treated with cytotoxic agents. The objective of this study is to evaluate the ECG changes after administration of 5-HT3 receptor antagonists and chemotherapeutic agents in children with cancer.
Procedure
Thirty-eight patients with an age range between 2 and 19 years receiving chemotherapy for solid tumors were included in the study. The patients received 5-HT3 receptor antagonists 30 min before antineoplastic agents in 83 chemotherapy days. Antiemetic therapy consisted of ondansetron in 43 and granisetron in 40 chemotherapy days. Twelve-leads ECGs were obtained four times at the first day of each chemotherapy: just before 30, 90 min, and 24 hr after 5-HT3 receptor antagonists were given. Rate, rhythm, PR interval, QRS duration, ST segment, the shortest (QTca) and the longest (QTcb) QTc intervals with QTc dispersion (QTcd) were all evaluated.
Results
We found a significant shortening of the PR interval and QRS complex durations in the granisetron group at 90th min and at 24th hr, respectively. Also, granisetron infusion caused a significant prolongation of the QTca interval at 90 min.
Conclusion
Although we observed minor ECG changes after 5-HT3 receptor antagonists and chemotherapy, neither dangerous rhythm disturbances nor serious ECG changes were seen. Pediatr Blood Cancer 2006; 47:567–571. © 2005 Wiley-Liss, Inc.
37 citations
TL;DR: The patient's risk of developing PONV could be reduced by considering the use of regional anesthesia, maintaining general anesthesia with propofol rather than with inhaled anesthetic agents, ensuring good intravenous hydration, and providing effective pain management using a multimodal approach.
37 citations
TL;DR: Improved prophylaxis of PONV following breast surgery is indicated by avoiding risk factors, and by using effective antiemetic agents in women scheduled for mastectomy (with axillary dissection).
Abstract: Breast surgery performed under general anaesthesia is associated with a high incidence of postoperative nausea and vomiting (PONV). Between 60% and 80% of patients undergoing mastectomy (with axillary dissection) experience PONV. Pharmacological approaches have been investigated to reduce PONV after breast surgery. Traditional antiemetics (droperidol and metoclopramide) are frequently used for the prevention of PONV during the first 24 hours after anaesthesia. The available non-traditional antiemetics that have been shown to be effective for prophylaxis against PONV are dexamethasone, clonidine, propofol and supplemental oxygen. Antiserotonins (ondansetron, granisetron, tropisetron, dolasetron and ramosetron) are highly effective for preventing PONV for 24 hours postoperatively, compared with traditional antiemetics. Ramosetron is effective for the long-term (up to 48 hours) prevention of PONV. Better results can be obtained by combining antiemetics, because they have different sites of action. Combination antiemetic therapy is often effective for preventing PONV after breast surgery. Combinations of an antiserotonin (granisetron or dolasetron) and droperidol or dexamethasone are more effective than monotherapy with antiserotonins. A non-pharmacological technique is acupuncture at the P6 (Nei-Kuan) point. Overall, these pharmacological and non-pharmacological approaches reduce the incidence of PONV following breast surgery. Most of the published trials indicate improved prophylaxis of PONV following breast surgery by avoiding risk factors, and by using effective antiemetic agents in women scheduled for mastectomy (with axillary dissection). The clinician must weigh the benefits of using pharmacological and non-pharmacological approaches for PONV against the risk of occurrence of adverse events.
35 citations
TL;DR: Ondansetron (4 mg IV) was more cost-effective than granisetron(1 mg per os) for routine antiemetic prophylaxis as part of a multimodal regimen in patients undergoing either outpatient or inpatient laparoscopic surgery.
Abstract: Based on comparative studies in patients receiving emetogenic chemotherapy, it has been suggested that granisetron would be more effective than ondansetron for the prevention of postdischarge nausea and vomiting (PDNV). However, there have been no direct comparisons of these two popular 5-HT3 antagonists with respect to PDNV and quality of recovery. We designed this randomized, double-blind study to compare the antiemetic efficacy of oral granisetron (1 mg) to a standard IV dose of ondansetron (4 mg) when administered for antiemetic prophylaxis as part of a multimodal regimen in a laparoscopic surgical population. A total of 220 patients undergoing laparoscopic surgery with a standardized general anesthetic technique were enrolled in this prospective study at two major medical centers. Patients were randomly assigned to one of two prophylactic treatment groups: the control (ondansetron) group received an oral placebo 1 h before surgery and ondansetron, 4 mg IV, at the end of the surgery, and the granisetron group received granisetron, 1 mg per os, 1 h before surgery, and normal saline, 2 mL IV, at the end of the surgery. The early recovery profiles, requirement for rescue antiemetics, incidence of PDNV, and the side effects were recorded over the 48 h study period. In addition, nausea scores were assessed using an 11-point verbal rating scale at specific intervals in the postoperative period. The quality of recovery and patient satisfaction scores were recorded at 48 h after surgery. The demographic characteristics were similar in the two prophylaxis treatment groups, as well as the recovery times to patient orientation, oral intake, and hospital discharge. The incidences of PDNV, requirements for rescue antiemetics, and quality of recovery did not differ between the two study groups. The antiemetic drug acquisition costs to achieve comparable patient satisfaction with ondansetron and granisetron were US 25.65 dollars and 47.05 dollars, respectively. Therefore, ondansetron (4 mg IV) was more cost-effective than granisetron (1 mg per os) for routine antiemetic prophylaxis as part of a multimodal regimen in patients undergoing either outpatient or inpatient laparoscopic surgery.
33 citations
TL;DR: Several other NK-1 receptor antagonists, including casopitant, vestipitant, netupitant, and SCH619734, are undergoing clinical evaluation for the prevention of CINV in patients with a variety of malignancies.
33 citations
TL;DR: Modeling and mutation studies suggest that granisetron plays its antagonist role by hindering the closure of the back wall of the binding cavity in type-3A serotonin receptors.
Abstract: A new homology model of type-3A serotonin receptors (5-HT3ARs) was built on the basis of the electron microscopic structure of the nicotinic acetylcholine receptor and with an agonist-free binding cavity. The new model was used to re-evaluate the interactions of granisetron, a 5-HT3AR antagonist. Docking of granisetron identified two possible binding modes, including a newly identified region for antagonists formed by loop B, C, and E residues. Amino acid residues L184−D189 in loop B were mutated to alanine, while Y143 and Y153 in loop E were mutated to phenylalanine. Mutation H185A resulted in no detectable granisetron binding, while D189A resulted in a 22-fold reduction in affinity. Y143F and Y153F decreased granisetron affinity to the same extent as Y143A and Y153A mutations, supporting the role of the OH groups of these tyrosines in loop E. Modeling and mutation studies suggest that granisetron plays its antagonist role by hindering the closure of the back wall of the binding cavity.
Journal Article•
TL;DR: Prophylactic combination antiemetic therapy of granisetron (40mcg/kg) dexamethasone (8mg) was found to be superior to individual therapy ofgranisetrons and ondansetron and combination therapy of ondANSetron (.1mg/kg] and dex amethas one ( 8mg) in middle ear surgery.
Abstract: Introduction : Our study focuses on post-operative nausea and vomiting (PONV) in middle ear surgery, a horrible experience to both doctors and patients. We compared the efficacy of granisetron and ondansetron alone and their combination with dexamethasone, for prevention of PONV in middle ear surgery. Methods: 125 patients (63 females, 62 males) with a age group between 10 to 60 years , who underwent middle ear surgery were randomly allocated and divided into 5 groups (25 patients in each group) according to the drug they receive i.e, Group-A (control group-no antiemetic), Group-B (granisetron 40mcg/kg), Group-C (granisetron 40mcg/kg + dexamethasone 8mg), Group-D (ondansetron .1mg/kg), Group-E (ondansetron .1mg/kg+ dexamethasone 8mg). After a standard protocol used in all of them, all the groups were evaluated for post-operative nausea , retching and vomiting and their side effects immediately at extubation for 24 hours of anesthesia. Results: The incidence of PONV is different in all groups i.e., maximum in group A (76%) followed by group D (28%), then group B (16%),then group E (12%) and minimum in group C (8%) and statistically significant (p <.001). The incidence of PONV was maximum during first 6 hours, but group B & group C showed higher incidence during first 12 hours whereas group D showed higher incidence during late postoperative period. Conclusion: Prophylactic combination antiemetic therapy of granisetron (40mcg/kg) dexamethasone (8mg) was found to be superior to individual therapy of granisetron and ondansetron and combination therapy of ondansetron (.1mg/kg) and dexamethasone (8mg) in middle ear surgery
TL;DR: It appears that patients at high risk of PONV who are treated prophylactically with combination 5- HT3RA/dexamethasone therapy are overall less likely to require rescue medication than if treated with 5-HT3RAs or dexameth asone alone.
Abstract: Objective:To assess the use of rescue antiemetic medication following 5-HT3 receptor antagonist (5-HT3RA) plus dexamethasone therapy versus monotherapy with a 5-HT3RA for prophylaxis of postoperative nausea and vomiting (PONV).Data Sources:Reports of randomized, controlled trials were identified via a MEDLINE search (1966–September 2005) using the key terms ondansetron, dolasetron, tropisetron, granisetron, 5-HT3, PONV, vomiting, emesis, and nausea.Study Selection and Data Extraction:Randomized, controlled trials of adult populations that had treatment arms comparing 5-HT3RA/dexamethasone combination therapy with 5-HT3RA or dexamethasone monotherapies versus placebo or 5-HT3RA versus dexamethasone or placebo were selected for analysis. Another criterion was that a proportion of patients required rescue medication 48 hours or less following surgery.Data Synthesis:Odds ratios (ORs) with 95% confidence interval were calculated to determine incidence rates for use of rescue medications within early (0–6 h), l...
Journal Article•
TL;DR: In this article, the authors compared the antiemetic effect of intravenous granisetron 3mg, ondansetron 4mg and metoclopramide 10mg in a randomized double blind study for prophylaxis of post operative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy under general anaesthesia.
Abstract: Nausea and vomiting is a common and distressing complication for patients with virtually all types of surgical procedures, its consequences being physical (like sweating, tachycardia, electrolyte imbalance) surgical (disruption of vascular anastamosis) and anaesthetic (aspiration pneumonitis). The aim of the present study was to compare the antiemetic effect of intravenous granisetron 3mg, ondansetron 4mg & metoclopramide 10mg in a randomized double blind study for prophylaxis of post operative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy under general anaesthesia. 60 patients (ASA I & II) undergoing laparoscopic cholecystectomy under general anaesthesia were randomly allocated into three equal groups. Group A (n=20) received 4mg ondansetron, Group B (n=20) 3mg granisetron and group C (n=20) metoclopramide 10mg. The drugs were diluted in 50ml normal saline and given intravenous slowly over 10mins before induction of anaesthesia. Anaesthesia procedure was common to all the patients. Emetic episodes in first 24 hours were recorded and compared in different study groups. Results were analyzed using chi square test. A value of p < 0.05 was considered to be significant. Emetic episodes were observed in 45% patients in group B, 70% patients in Group-A and 95% patients in group C. To conclude, minimal emetic episodes were observed in early post-operative period (1-12hrs) in patients who had received intravenous granisetron in comparison to ondansetron and metoclopramide. However, after 12 hours emesis free periods were statistically insignificant between group A and B while patients in group C had no antiemetic effect.
TL;DR: A long surgical period may have great impact on the PONV in women who undergo gynecologic laparoscopic surgery, which implies the need for skilled gynecological laparoscopists.
TL;DR: It is concluded that the risk of postoperative nausea and vomiting is less with cyclizine and granisetron given together than with either given alone.
Abstract: We conducted a randomised double-blinded study of 960 women undergoing day-case surgery to determine whether combination anti-emetic therapy of granisetron and cyclizine was more effective at decreasing the incidence of postoperative nausea and vomiting than these agents used alone. The women were randomly allocated to three groups to receive intravenous granisetron 1 mg, cyclizine 50 mg or both before induction of general anaesthesia. The incidence of postoperative nausea and vomiting was 77/322 (24%) in the granisetron group, 73/316 (23%) in the cyclizine group and 53/322 (17%) in those women given both drugs (p = 0.04). There was no difference in the requirement for rescue anti-emetic drugs. There were no differences in the anaesthetic techniques used in the three groups. We conclude that the risk of postoperative nausea and vomiting is less with cyclizine and granisetron given together than with either given alone.
TL;DR: The clinical pharmacology of 5-HT3 antagonists and recommendations for nursing management of PONV are explained and granisetron, a 5- HT3 receptor antagonist, is provided, which is less likely to adversely interact with other medications.
TL;DR: It is suggested that a combined 5-HT3-receptor antagonist/5-HT4-recept agonist, like zacopride, may be useful against both acute and delayed emesis induced by cancer chemotherapy.
TL;DR: Data support the use of metopimazine as add-on therapy in the treatment of acute emesis in patients receiving moderately emetogenic chemotherapy who are refractory to initial therapy or unable to take corticosteroids, as well as roles which are also suggested for dopamine receptor antagonists in guidelines, as is their potential use in rescue therapy for patients with breakthrough symptoms.
Abstract: Summary|Metopimazine (Vogalene®) is a dopamine D 2 receptor antagonist that has been used in France for many years for the prevention and treatment of nausea and vomiting. Guidelines suggest a role for dopamine receptor antagonists in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy and as add-on therapy in refractory cases; recent data on sublingual metopimazine suggest it may have a role as an alternative to ondansetron in the prevention of delayed CINV in patients receiving moderately to highly emetogenic non-cisplatin-based chemotherapy. Trials comparing metopimazine with other drugs used in the prevention of delayed CINV would be of interest. Data also support the use of metopimazine as add-on therapy in the treatment of acute emesis in patients receiving moderately emetogenic chemotherapy who are refractory to initial therapy or unable to take corticosteroids, roles which are also suggested for dopamine receptor antagonists in guidelines, as is their potential use in rescue therapy for patients with breakthrough symptoms.Pharmacologic PropertiesMetopimazine is a phenothiazine derivative with anti-dopaminergic activity. It has a high affinity for dopamine D 2 receptors (and also α 1 -adrenoceptors and histamine H 1 receptors) but no affinity for serotonin 5-HT 3 receptors. It exerts its antiemetic effects via the chemoreceptor trigger zone. Although metopimazine itself can cross the blood-brain barrier, its acid metabolite, which is the predominant circulating form of the drug, crosses to a very limited extent, and extrapyramidal effects and effects on prolactin are uncommon. Metopimazine can occasionally be associated with orthostatic hypotension, which probably relates to its affinity for the α 1 -adrenoceptor.Peak serum concentrations are reached within 60 minutes after fasting oral administration (≈20 minutes for sublingual tablets). The bioavailability of oral metopimazine is 19–34%. Oral absorption is reduced by food. Metopimazine is rapidly metabolized to its active acid metabolite, which constitutes approximately 78–89% of the circulating drug. Approximately 30% of a dose is recovered in the urine (mostly as the acid form), and the elimination half-life of the parent drug is approximately 4.5 hours.Therapeutic EfficacyMetopimazine has been evaluated for the prevention of acute or delayed CINV in adults in several randomized, controlled trials, some of which were performed a number of years ago and used treatment regimens that differ from current recommendations. In the earliest studies (performed in the 1970s and using different endpoints to later trials), the overall (and possibly acute) efficacy of oral metopimazine in the reduction of severity of CINV was superior to that of placebo in patients receiving low to highly emetogenic non-cisplatin-based chemotherapy, and similar to that of prochlorperazine in patients receiving fluorouracil.Results from trials performed since 1997 (which each evaluated similar endpoints) indicated that the addition of intravenous metopimazine to ondansetron plus methylprednisolone significantly increased antiemetic efficacy in the acute phase compared to ondansetron plus methylprednisolone in patients receiving cisplatin who were refractory to the dual therapy (87% vs 75% of patients experienced no acute emesis); also that intravenous metopimazine plus ondansetron was significantly more effective than ondansetron alone at preventing acute emesis in patients receiving highly emetogenic (cisplatin-based) chemotherapy. Oral metopimazine combined with prednisolone was significantly less effective than intravenous granisetron in the acute setting (comparison of all response categories), but more effective than granisetron (both in terms of overall response categories and complete response rate) in the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy.Based on two recent studies specifically designed to evaluate efficacy in the prevention of delayed emesis, sublingual metopimazine was as effective as ondansetron when administered as monotherapy, and at least as effective when both drugs were coadministered with methylprednisolone, in patients receiving moderately to highly emetogenic (generally non-cisplatin-based) chemotherapy. The percentages of patients who experienced no delayed emesis (and ≤1 episode of nausea) when treated with metopimazine or metopimazine plus methylprednisolone were 53% and 74% compared with 50% and 58% for recipients of ondansetron or ondansetron plus methylprednisolone. Additional supportive data for the effectiveness of metopimazine in combination with other antiemetic agents (particularly ondansetron) for the prevention of delayed nausea and vomiting are available from studies that were not specifically designed to examine delayed emesis.TolerabilityMetopimazine is generally well tolerated. In CINV trials, the overall incidence of adverse events with metopimazine monotherapy was similar to that seen with placebo and with ondansetron; however, metopimazine was associated with significantly fewer gastrointestinal adverse events than ondansetron.The most common adverse events reported with sublingual metopimazine monotherapy in a large clinical trial in CINV included constipation, diarrhea, abdominal pain, headache, and asthenia (and also alopecia and mucositis, which were most probably related to the chemotherapy patients had received).Based on a summary of periodic safety update reports, the adverse events most frequently reported with metopimazine (all formulations; cancer and non-cancer indications) include somnolence, heartburn, dry mouth, diarrhea, constipation, vertigo, tachycardia, dysuria, headache, and pruritus. Metopimazine can be associated with orthostatic hypotension at high dosages. Extrapyramidal symptoms, including dyskinesias, are very uncommon.
01 Jan 2006
TL;DR: The purpose of this study was to compare the efficacy and safety of serotonin type 3 receptor antagonists (5-HT3RA) in combination with a ReliefBand (Woodside) to diagnose and treat post-operative nausea and vomiting.
Abstract: Purpose: Post-operative nausea and vomiting (PONV) is commonly experienced by patients after surgical procedures. Among the highest risk group for PONV are women undergoing abdominal procedures. The purpose of this study was to compare the efficacy and safety of serotonin type 3 receptor antagonists (5-HT3RA) in combination with a ReliefBand (Woodside
TL;DR: It is clear that the results of the present study should be confirmed in a population study involving a larger number of subjects addressing the genetic variations of drug metabolizing enzymes, drug receptors, and drug transporters.
Abstract: BACKGROUND Docetaxel, which undergoes hepatic metabolism via cytochrome P450 3A4, is a promising anticancer agent. Toxicity is serious problem, however, because it is difficult to predict the cytochrome P450 3A4 activity of the drug. Moreover, drug-drug interactions involving cytochrome P450 3A4 enzymes are important. Granisetron, a selective antagonist of the 5-hydroxytryptamine3 receptor, also undergoes hepatic metabolism via cytochrome P450 3A4. In this study, we investigated the influence of granisetron on the pharmacokinetics and pharmacodynamics of docetaxel in Asian patients with lung cancer. METHODS Six patients with advanced lung cancer were treated with doses of docetaxel (60 mg/m2). In the first course of treatment, no antiemetic agents were administered. In the second course, all patients received 3.0 mg of granisetron before 30-minute administration of docetaxel. In each of the treatment courses, blood samples (5 mL) were obtained for pharmacokinetic study at the following times: 0, 0.5, 1.5, 2.0, 3.0, 5.0, 8.0, and 24 hours after the start of the docetaxel infusion. RESULTS Six patients were enrolled in this pharmacokinetics study. The mean +/- SD systemic clearance of docetaxel administered alone or in combination with granisetron was 32.9 +/ - 8.3 and 28.2 +/- 5.9, respectively. The area under the concentration-versus-time curve of plasma docetaxel (alone or in combination with granisetron) ranged from 1.355 to 2.773 and 1.647 to 3.079 microg x h/mL (mean +/- SD: 1.936 +/- 0.541 and 2.219 +/- 0.510 microg x h/mL), respectively. There was no significant difference in mean residence time (or invariance of residence time) between the single dose of docetaxel and the combination of docetaxel and granisetron. DISCUSSION We found no significant difference in the pharmacokinetic and pharmacodynamic parameters of docetaxel between the single dose of docetaxel and the combination of docetaxel and granisetron. However, a wide interindividual variation existed in cytochrome P450 3A4 activity. It is clear that the results of the present study should be confirmed in a population study involving a larger number of subjects addressing the genetic variations of drug metabolizing enzymes, drug receptors, and drug transporters.
TL;DR: The minimum effective dose of granisetron for the treatment of PONV in women undergoing breast surgery was 20 microg/kg, and increasing the granisetsetron dose to 80 microG/kg provided no further benefit.
Abstract: Background: p ]Women undergoing general anaesthesia for breast surgery are especially at risk of experiencing postoperative nausea and vomiting (PONV). This study was undertaken to assess the efficacy of granisetron, a selective serotonin type 3 receptor antagonist, for the treatment of postoperative nausea and vomiting after breast surgery.
Patent•
17 May 2006
TL;DR: The Granisetron cataplasm with transdermal administration has no first pass effect, reduced and constant systemic blood medicine concentration, less side effect, raised compliance and other advantages as mentioned in this paper.
Abstract: The present invention relates to medicine technology, and is Granisetron cataplasm as 5-HT3 receptor agonist in new form. Granisetron is applied clinically in preventing and treating nausea, vomiting, etc caused by cytotoxicity treatment, and available Granisetron preparation forms have some demerits. The present invention prepares Granisetron into cataplasm with the hydrochloride or free alkali of Granisetron as main medicine component and some supplementary materials. The Granisetron cataplasm with transdermal administration has no first pass effect, reduced and constant systemic blood medicine concentration, less side effect, raised compliance and other advantages.
Journal Article•
Journal Article•
TL;DR: In addition to conventional neurotransmitters S and D, NA is also worthy of attention in connection with nausea/emesis, and a significant difference was demonstrated for NA on the day before chemotherapy, and between effective and non-effective patients receiving anti-emetic treatment.
Abstract: A clinical study was conducted to investigate the relationship between nausea/emesis after chemotherapy for lung cancer (docetaxel 60 mg/m(2), cisplatin 80 mg/m(2)) and blood serotonin (S), blood catecholamine (adrenaline) (A), noradrenaline (NA) and dopamine (D) in effective and non-effective patients treated with anti-emetic agents. All 37 patients received preventive combination administration of granisetron (GR) 3 mg, methylprednisolone 500 mg and metoclopramide (ME) 40 mg immediately before chemotherapy, followed by GR 3 mg and ME 40 mg on Day 2 and 3. Sixteen patients who were classified as emotionally unstable according to the YG character test additionally received prochlorperazine 15 mg thrice daily starting after their last meal prior to chemotherapy, until nausea/emesis disappeared. Blood concentration was measured on the day before chemotherapy and on Day 2, 4, and 14 after administration of the anticancer agents. As a result, a significant difference was demonstrated for NA on the day before chemotherapy (p<0.05), NA on Day 14 (p<0.01) and D on Day 14 (p<0.01) between effective and non-effective patients receiving anti-emetic treatment. In addition to conventional neurotransmitters S and D, NA is also worthy of attention in connection with nausea/emesis.
Journal Article•
TL;DR: In this paper, the authors reviewed relevant data for recommended antiemetics (5-hydroxytryptamine3-receptor antagonists, neurokinin-1 antagonists and corticosteroids) to assist in the selection of an appropriate agent for this subgroup of patients.
Abstract: The incidence of cancer is highest in people over 65 years of age, yet this population is not well represented in clinical trials for antiemetic therapies. Cytotoxic-induced nausea and vomiting remain two of the most distressing side effects for patients; however, the lack of adequate trial data has meant that specific recommendations for the appropriate use of antiemetics in the elderly are lacking. Consequently, clinicians must adjust the available recommendations to their elderly patients on an individual patient basis. However, declining organ function and frequent comorbid conditions mean that this patient group may be at risk of suboptimal antiemetic therapy and/or drug–drug interactions. This article will review relevant data for recommended antiemetics – 5-hydroxytryptamine3-receptor antagonists, neurokinin-1 antagonists and corticosteroids – to assist in the selection of an appropriate agent for this subgroup of patients.