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- Netupitant-palonosetron combination approved by FDA. [Journal Article]
- Am J Health Syst Pharm 2014 Dec 1; 71(23):2000.
- Separation mechanisms for palonosetron stereoisomers at different chiral selector concentrations in MEKC. [JOURNAL ARTICLE]
- Electrophoresis 2014 Nov 18.
The separation mechanisms for palonosetron (PALO) stereoisomers in MEKC using sodium cholate (SC) as surfactant and chiral selector have been studied, in a wide range of concentrations below and above the CMC. It was found that SC micelles only provide chirally selective recognition for 3a carbon chiral center in PALO molecules. The resolution of the configurations of 2 carbon chiral center is achieved by the difference of mobility in continuous phase. A schematic diagram depicting the separation mechanisms and the corresponding migration orders among all of four stereoisomers was proposed based on the measured separation parameters. A MEKC method to achieve the complete separation of four stereoisomers in very short time using a very low chiral selector concentration, instead of high concentrations generally considered, was developed based on the understanding of the mechanisms. This article is protected by copyright. All rights reserved.
- Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages in postoperative ileus. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Nov 6.
Postoperative ileus (POI) is induced by intestinal muscularis inflammation. The present study aimed to clarify the therapeutic action of 5-hydroxytryptamine 3 receptor (5-HT3 R) antagonists against POI.We administered three 5-HT3 R antagonists subcutaneously (s.q.) (ondansetron, tropisetron and palonosetron) to a mouse model of POI induced by surgical intestinal manipulation (IM). Immunohistochemistry, intestinal transit, inflammatory mediators mRNA expression and 5-HT content measurement were performed. In some experiments, 5-HT3aR null mice were used.Three 5-HT3 antagonists significantly reduced the IM-induced infiltration of inflammatory CD68-positive macrophages and MPO-stained neutrophils, indicating anti-inflammatory actions against POI. Ondansetron-induced anti-inflammatory action was disappeared in 5-HT3aR KO mice. Ondansetron inhibited the expression of MCP-1, IL-1β, IL-6, TNF-α and iNOS mRNAs upregulated by IM, and also ameliorated gastrointestinal transit that was delayed by IM. Peritoneal macrophages expressed 5-HT3 R, whereas most infiltrative monocyte-derived macrophages did not. IM stimulation increased the 5-HT content of peritoneal lavage fluid, which in turn upregulated the mRNA expression of proinflammatory cytokines in peritoneal macrophages. 5-HT3 R immunohistochemical localization suggests that ondansetron suppressed the expression of these mRNAs in activated peritoneal macrophages that adhered to the serosal region of the inflamed intestinal wall.5-HT3 R antagonists had anti-inflammatory effects and recovered the delayed gastrointestinal transit by IM. 5-HT3 R antagonists are a useful therapeutic agent against POI. Anti-inflammatory actions were induced by 5-HT3 R antagonists that mainly targeted peritoneal macrophages expressing 5-HT3 R.
- Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting. [JOURNAL ARTICLE]
- Future Oncol 2014 Oct 31.:1-13.
ABSTRACT Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines.
- Palonosetron for the treatment of chemotherapy-induced nausea and vomiting. [Journal Article]
- Expert Opin Pharmacother 2014 Dec; 15(17):2599-608.
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists has been a major factor in the improvement of the prevention of chemotherapy-induced acute and delayed emesis. Palonosetron , a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in this drug class.Palonosetron's chemistry, pharmacodynamics, pharmacokinetics, metabolism, clinical efficacy, including comparison with other antiemetics, role in controlling nausea, potential role in multi-day chemotherapy and bone marrow transplantation, and overall safety are discussed.The clinical data in the literature have established palonosetron as the 5-HT3 receptor antagonist of choice in terms of efficacy and safety for the prevention of CINV for patients receiving moderately or highly emetogenic chemotherapy. Three international guidelines have listed palonosetron as the preferred 5-HT3 receptor antagonist. Due to its higher efficacy, the use of palonosetron may be more cost effective compared to the generic first-generation 5-HT3 receptor antagonists. Clinical organizations' pharmacy and formulary committees should consider efficacy when making recommendations for agents for the prevention of CINV.
- Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas. [Journal Article]
- Acta Otolaryngol 2014 Nov; 134(11):1198-204.
Abstract Conclusion: Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma.A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines.Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition.The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.
- Evaluation of the ability of continuous palonosetron infusion, using a patient-controlled analgesia device, to reduce postoperative nausea and vomiting. [Journal Article]
- Korean J Anesthesiol 2014 Aug; 67(2):110-4.
The efficacy of palonosetron in preventing postoperative nausea and vomiting (PONV), as well as chemotherapy-induced nausea and vomiting, has already been demonstrated in multiple clinical studies. The purpose of this study was to determine whether continuous infusion of palonosetron following single injection could reduce PONV to a greater extent than single injection only of palonosetron.In total, 132 women were enrolled in the study. All subjects were over the age of 20 years and were scheduled to undergo gynecologic laparoscopic surgery. Patients were randomly allocated into two groups. In both groups, patients received 0.075 mg of palonosetron intravenously, immediately before induction of anesthesia. In the continuous palonosetron infusion group, 0.075 mg (1.5 ml) of palonosetron was added to the patient-controlled analgesia device. In the single-injection palonosetron group, 1.5 ml of normal saline was added.The incidence of PONV 24 hours postoperatively was significantly lower in the continuous palonosetron infusion group than the single-injection palonosetron group (31.8 vs. 56.1%, P = 0.009).Continuous palonosetron infusion, following single injection, reduces the incidence of PONV compared with single injection only.
- Palonosetron in the management of chemotherapy-induced nausea and vomiting in patients receiving multiple-day chemotherapy. [Journal Article, Review]
- Cancer Manag Res 2014.:329-37.
Prevention of chemotherapy-induced nausea and vomiting (CINV) is a key component of treatment for patients with cancer. Guidelines are available to assist prescribers in the management of CINV associated with single-day chemotherapy regimens. However, currently there are no clear guidelines for management of CINV in patients receiving multiple-day chemotherapy regimens. Serotonin (5-HT3) receptor antagonists are a mainstay in preventing CINV, and palonosetron, given its longer half-life and duration of action relative to other 5-HT3 receptor antagonists, may be a useful option for managing CINV in multiple-day chemotherapy. Here we provide an overview of CINV and CINV treatment options, with a focus on palonosetron. We describe existing challenges in managing CINV, and discuss two patients receiving multiple-day chemotherapy, in whom CINV was managed successfully with palonosetron.
- Addressing the value of novel therapies in chemotherapy-induced nausea and vomiting. [JOURNAL ARTICLE]
- Expert Rev Pharmacoecon Outcomes Res 2014 Sep 16.:1-10.
Chemotherapy-induced nausea and vomiting (CINV) is a troubling side effect of cancer treatment and is often poorly controlled. As a consequence, CINV is associated with substantially increased costs of care and significant interference with patients' lives. Inadequate control over CINV results from factors that include failure to provide guideline-adherent prophylactic medication and limitations in available therapies. Newer serotonin receptor antagonists, such as palonosetron, and addition of neurokinin-1 (NK-1) receptor antagonists to treatment have significantly decreased both acute and delayed CINV. A fixed-dose combination of palonosetron and a new NK-1 receptor, netupitant, is significantly superior to palonosetron alone and has small, but consistent, numerical advantages over aprepitant plus palonosetron for prevention of CINV. The combination of a serotonin receptor antagonist plus an NK-1 receptor antagonist has been shown to be cost-effective for prevention of CINV and the availability of a fixed-dose combination of netupitant and palonosetron may enhance this benefit.
- 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects. [JOURNAL ARTICLE]
- Expert Opin Drug Saf 2014 Sep 6.:1-16.
Introduction: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients. Areas covered: The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron. Expert opinion: Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapy-induced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.