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Aprepitant

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https://www.readbyqxmd.com/read/29330211/olanzapine-based-triple-regimens-versus-neurokinin-1-receptor-antagonist-based-triple-regimens-in-preventing-chemotherapy-induced-nausea-and-vomiting-associated-with-highly-emetogenic-chemotherapy-a-network-meta-analysis
#1
Zhonghan Zhang, Yaxiong Zhang, Gang Chen, Shaodong Hong, Yunpeng Yang, Wenfeng Fang, Fan Luo, Xi Chen, Yuxiang Ma, Yuanyuan Zhao, Jianhua Zhan, Cong Xue, Xue Hou, Ting Zhou, Shuxiang Ma, Fangfang Gao, Yan Huang, Likun Chen, Ningning Zhou, Hongyun Zhao, Li Zhang
BACKGROUND: The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear. MATERIALS AND METHODS: We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant...
January 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29315462/aprepitant-as-a-fourth-antiemetic-prophylactic-strategy-in-high-risk-patients-a-double-blind-randomized-trial
#2
L C de Morais, A M Sousa, G F Flora, T R Grigio, G M N Guimarães, H A Ashmawi
BACKGROUND: Post-operative nausea and vomiting (PONV) is one of the most important causes of patient discomfort after laparoscopic surgeries despite the use of a multimodal pharmacological approach. This study assessed whether the addition of aprepitant to a multimodal regimen would further decrease the incidence of PONV in high-risk patients. METHODS: Apfel-score three or four patients, scheduled for laparoscopic procedures to treat abdominal or pelvic cancer, were randomized to receive oral starch (control group) or 80 mg of oral aprepitant (treatment group) before induction of anaesthesia in a double-blind study...
January 7, 2018: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29248965/effectiveness-of-olanzapine-in-patients-who-fail-therapy-with-aprepitant-while-receiving-highly-emetogenic-chemotherapy
#3
Nikita Mehra, Prasanth Ganesan, Trivadi S Ganesan, Surendran Veeriah, Abirami Boopathy, Venkatraman Radhakrishnan, Manikandan Dhanushkodi, Swaminathan Rajaraman, Sevaluxmy Ganesharajah, Tenali Gnana Sagar
Chemotherapy-induced nausea-vomiting (CINV) compromises the quality of life of patients with cancer. We present data on the effectiveness of olanzapine after failure of aprepitant in patients receiving highly emetogenic chemotherapy (HEC). A single-center prospective study was conducted, where patients ≥ 18 years who failed aprepitant, palonosetron, dexamethasone (APD) received olanzapine, palonosetron and dexamethasone (OPD) in the subsequent cycle of HEC. Failure of APD was defined as occurrence of ≥ grade 2 acute and/or delayed nausea ± vomiting...
December 16, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29245084/application-of-analytical-quality-by-design-principles-for-the-determination-of-alkyl-p-toluenesulfonates-impurities-in-aprepitant-by-hplc-validation-using-total-error-concept
#4
Constantinos K Zacharis, Elli Vastardi
In the research presented we report the development of a simple and robust liquid chromatographic method for the quantification of two genotoxic alkyl sulphonate impurities (namely methyl p-toluenesulfonate and isopropyl p-toluenesulfonate) in Aprepitant API substances using the Analytical Quality by Design (AQbD) approach. Following the steps of AQbD protocol, the selected critical method attributes (CMAs) were the separation criterions between the critical peak pairs, the analysis time and the peak efficiencies of the analytes...
December 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29244998/applicability-of-the-national-comprehensive-cancer-network-multinational-association-of-supportive-care-in-cancer-guidelines-for-prevention-and-management-of-chemotherapy-induced-nausea-and-vomiting-in-southeast-asia-a-consensus-statement
#5
Alexandre Chan, Matin M Abdullah, Wan Zamaniah B Wan Ishak, Annielyn B Ong-Cornel, Antonio H Villalon, Ravindran Kanesvaran
A meeting of regional experts was convened in Manila, Philippines, to develop a resource-stratified chemotherapy-induced nausea and vomiting (CINV) management guideline. In patients treated with highly emetogenic chemotherapy in general clinical settings, triple therapy with a serotonin (5-hydroxytryptamine-3 [5-HT3]) antagonist (preferably palonosetron), dexamethasone, and aprepitant is recommended for acute CINV prevention. In resource-restricted settings, triple therapy is still recommended, although a 5-HT3 antagonist other than palonosetron may be used...
December 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/29182791/substance-p-antagonist-aprepitant-shows-no-additive-effect-compared-with-standardized-topical-treatment-alone-in-patients-with-atopic-dermatitis
#6
Louise Lönndahl, Mikael Holst, Maria Bradley, Hassan Killasli, Johan Heilborn, Martin A Hall, Elvar Theodorsson, Jadwiga Holmberg, Klas Nordlind
Atopic dermatitis (AD) is a chronic, itchy, inflammatory skin disorder that may worsen due to stress and anxiety. Tachykinins have been suggested to be involved in the inflammation in AD, as well as pruritus, stress and anxiety. Aprepitant is a NK-1 receptor antagonist. This open randomized trial evaluated the effect of aprepitant added to topical treatment in adult patients with moderate-severe AD. The treatment group (n = 19) received 80 mg/day aprepitant for 7 days as a supplement to standardized topical treatment with a moderately strong steroid and a moisturizer...
November 28, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29147855/phase-ii-study-of-palonosetron-aprepitant-and-dexamethasone-to-prevent-nausea-and-vomiting-induced-by-multiple-day-emetogenic-chemotherapy
#7
Takeshi Ioroi, Junya Furukawa, Manabu Kume, Sachi Hirata, Yuko Utsubo, Naomi Mizuta, Hideaki Miyake, Masato Fujisawa, Midori Hirai
PURPOSE: This study aimed to determine the antiemetic efficacy and safety of palonosetron, aprepitant and dexamethasone in patients with testicular germ cell tumours (TGCTs) receiving 5-day cisplatin-based combination chemotherapy. METHODS: In this open-label, single-arm, single-centre study, the antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2-7 and dexamethasone 6.6 mg on days 1-7. The primary endpoint was complete response (CR; no vomiting/retching or rescue medication) in the overall period (0-240 h), and secondary endpoints included complete protection (CP; defined as CR and no more than mild nausea) and total control (TC; defined as CR and no nausea)...
November 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29130344/neurokinin-1-receptor-antagonists-in-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-focus-on-fosaprepitant
#8
Bernardo L Rapoport, Karin Jordan, Cindy Weinstein
Chemotherapy-induced nausea and vomiting (CINV) remains a challenge in cancer care. Improved understanding of CINV pathophysiology has triggered the development of new antiemetic therapeutic options, such as selective neurokinin-1 (NK1) receptor antagonists (RAs), which effectively prevent CINV when added to a standard antiemetic regimen (serotonin-3 RA and dexamethasone). Aprepitant and its water-soluble prodrug, fosaprepitant dimeglumine, are the most widely used NK1 RAs, with extensive clinical use worldwide...
November 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29111115/aprepitant-has-mixed-effects-on-nausea-and-reduces-other-symptoms-in-patients-with-gastroparesis-and-related-disorders
#9
Pankaj J Pasricha, Katherine P Yates, Irene Sarosiek, Richard W McCallum, Thomas L Abell, Kenneth L Koch, Linda Anh B Nguyen, William J Snape, William L Hasler, John O Clarke, Sameer Dhalla, Ellen M Stein, Linda A Lee, Laura A Miriel, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, James Tonascia, Frank A Hamilton, Henry P Parkman
BACKGROUND & AIMS: There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome. METHODS: We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months...
October 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29092012/a-randomized-phase-3-study-evaluating-the-efficacy-of-single-dose-nepa-a-fixed-antiemetic-combination-of-netupitant-and-palonosetron-versus-an-aprepitant-regimen-for-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-receiving-highly-emetogenic
#10
L Zhang, S Lu, J Feng, A Dechaphunkul, J Chang, D Wang, S Chessari, C Lanzarotti, K Jordan, M Aapro
Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared to PALO in cisplatin and anthracycline/cyclophosphamide-based settings...
October 28, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29090385/phase-ii-open-label-pilot-trial-of-aprepitant-and-palonosetron-for-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-receiving-moderately-emetogenic-folfox-chemotherapy-for-the-treatment-of-colorectal-cancer
#11
Joseph S Bubalo, Jon D Herrington, Marc Takemoto, Patricia Willman, Michael S Edwards, Casey Williams, Alan Fisher, Alison Palumbo, Eric Chen, Charles Blanke, Charles D Lopez
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients. METHODS: Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3...
October 31, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29075004/from-receptor-binding-kinetics-to-signal-transduction-a-missing-link-in-predicting-in-vivo-drug-action
#12
Indira Nederpelt, Maria Kuzikov, Wilbert E A de Witte, Patrick Schnider, Bruno Tuijt, Sheraz Gul, Adriaan P IJzerman, Elizabeth C M de Lange, Laura H Heitman
An important question in drug discovery is how to overcome the significant challenge of high drug attrition rates due to lack of efficacy and safety. A missing link in the understanding of determinants for drug efficacy is the relation between drug-target binding kinetics and signal transduction, particularly in the physiological context of (multiple) endogenous ligands. We hypothesized that the kinetic binding parameters of both drug and endogenous ligand play a crucial role in determining cellular responses, using the NK1 receptor as a model system...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29061362/efficacy-of-aprepitant-for-chop-chemotherapy-induced-nausea-vomiting-and-anorexia
#13
Mihoko Morita, Shinji Kishi, Miyuki Ookura, Yasufumi Matsuda, Katsunori Tai, Takahiro Yamauchi, Takanori Ueda
The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic...
September 23, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29057261/aprepitant-for-the-treatment-of-chronic-refractory-pruritus
#14
REVIEW
Alice He, Jihad M Alhariri, Ronald J Sweren, Madan M Kwatra, Shawn G Kwatra
Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29056150/substance-p-and-the-neurokinin-1-receptor-the-new-crf
#15
Jesse R Schank, Markus Heilig
Substance P (SP) is an 11-amino acid neuropeptide of the tachykinin family that preferentially activates the neurokinin-1 receptor (NK1R). First isolated 85 years ago and sequenced 40 years later, SP has been extensively studied. Early studies identified a role for SP and the NK1R in contraction of intestinal smooth muscle, central pain processing, and neurogenic inflammation. An FDA-approved NK1R antagonist, aprepitant, is used clinically for the treatment of chemotherapy-induced nausea, as the NK1R influences the activity of the brain stem emesis centers...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29043811/investigation-of-the-intra-and-interlaboratory-reproducibility-of-a-small-scale-standardized-supersaturation-and-precipitation-method
#16
Jakob Plum, Cecilie M Madsen, Alexandra Teleki, Jan Bevernage, Claudia da Costa Mathews, Eva M Karlsson, Sara Carlert, Rene Holm, Thomas Müller, Wayne Matthews, Alice Sayers, Krista Ojala, Konstantin Tsinsman, Ram Lingamaneni, Christel As Bergström, Thomas Rades, Anette Müllertz
The high number of poorly water-soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g., the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation...
November 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29039073/a-double-blind-randomized-phase-ii-dose-finding-study-of-olanzapine-10%C3%A2-mg-or-5%C3%A2-mg-for-the-prophylaxis-of-emesis-induced-by-highly-emetogenic-cisplatin-based-chemotherapy
#17
Takako Yanai, Satoru Iwasa, Hironobu Hashimoto, Fumiyoshi Ohyanagi, Tomomi Takiguchi, Koji Takeda, Masahiko Nakao, Hiroshi Sakai, Toshiaki Nakayama, Koichi Minato, Takahiro Arai, Kenichi Suzuki, Yasuhiro Shimada, Kengo Nagashima, Hiroyuki Terakado, Noboru Yamamoto
PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). METHODS: A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m(2))...
October 16, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29031010/evaluation-of-aprepitant-for-acute-chemotherapy-induced-nausea-and-vomiting-in-children-and-adolescents-with-acute-lymphoblastic-leukemia-receiving-high-dose-methotrexate
#18
Femi Felix-Ukwu, Kate Reichert, M Brooke Bernhardt, Eric S Schafer, Amanda Berger
BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) negatively impacts patients' quality of life. The emetogenicity of high-dose methotrexate in children and adolescents with cancer is incompletely characterized. At our institution, a number of patients with acute lymphoblastic leukemia (ALL) have received aprepitant with courses of high-dose methotrexate after poor CINV control with prior courses. PROCEDURE: We conducted a retrospective cohort analysis on patients with ALL who received methotrexate 5 g/m(2) /dose with and without concomitant aprepitant at Texas...
October 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29022160/a-catalyst-from-burkholderia-cenocepacia-for-efficient-anti-prelog-s-bioreduction-of-3-5-bis-trifluoromethyl-acetophenone
#19
Songzhu Yu, Hongxia Li, Yan Lu, Guojun Zheng
(R)-3, 5-Bis(trifluoromethyl)phenyl ethanol is a key chiral intermediate for the synthesis of aprepitant. Through a genome mining approach, an NADPH-dependent short-chain dehydrogenases derived from Burkholderia cenocepacia (Bc-SDR) was discovered with excellent anti-Prelog's stereoselectivity of reducing 3, 5-bis(trifluoromethyl) acetophenone. The enzyme with 247 amino acids was successfully expressed in Escherichia coli and the molecular weight was about 26 kDa. Optimization of reaction conditions showed that the optimum temperature and pH of the enzyme was 25 °C and pH 7...
October 12, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28987539/statistical-investigation-of-the-full-concentration-range-of-fasted-and-fed-simulated-intestinal-fluid-on-the-equilibrium-solubility-of-oral-drugs
#20
Jeremy Perrier, Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin Halbert
Upon oral administration the solubility of a drug in intestinal fluid is a key property influencing bioavailability. It is also recognised that simple aqueous solubility does not reflect intestinal solubility and to optimise in vitro investigations simulated intestinal media systems have been developed. Simulated intestinal media which can mimic either the fasted or fed state consists of multiple components each of which either singly or in combination may influence drug solubility, a property that can be investigated by a statistical design of experiment technique...
October 5, 2017: European Journal of Pharmaceutical Sciences
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