DOCSLIB.ORG

Use and Cardiovascular Safety of Transdermal and Other Granisetron Preparations in Cancer Management

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Use and Cardiovascular Safety of Transdermal and Other Granisetron Preparations in Cancer Management Cancer Management and Research Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management 1 Jay W Mason Abstract: 5-HT3 antagonists have been available as oral and intravenous preparations for Thomas E Moon2 decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and 1School of Medicine, University of Utah, Salt Lake City, UT, these preparations have been shown to have less potential to prolong QT than other drugs in 2Tarizona eHealth Services, Inc, the class. Emeryville, CA, USA Keywords: chemotherapy-induced nausea, vomiting, granisetron, QT prolongation Introduction Problem of chemotherapy-induced nausea and vomiting For personal use only. Chemotherapy-induced nausea and vomiting (CINV) occurs in 10%–90% of patients, depending on the emetic risk of the chemotherapeutic agent.1,2 There is a consider- able cost involved, not only for the expense of hospitalization and the direct treatment of CINV, but also because of the loss of workdays and the consequences of delayed 3–7 chemotherapy administration. There is consistent evidence that 5-HT3 antagonist antiemetic therapy has improved this problem without increasing the cost.3–7 Unmet needs in CINV treatment Delayed nausea and vomiting occurring hours or days after chemotherapy, either as a result of reduced plasma concentrations of prophylactic antiemetics administered at the time of chemotherapy, or inefficacy of ongoing oral antiemetic medications, is a Cancer Management and Research downloaded from https://www.dovepress.com/ by 54.70.40.11 on 17-Nov-2018 significant management problem.3,8 Palonosetron, due to its long half-life, provided a potential solution to this problem,9 yet despite its introduction, the problem continues to adversely affect the quality of life of chemotherapy recipients.10 An important objec- tive of the granisetron transdermal (TD) delivery system is maintenance of effective plasma concentration of granisetron during and for several days after administration of chemotherapy. Oral and intravenous (IV) administration of granisetron and other antiemetics is problematic in some patients. Because the oral route is complicated by variable bioavail- ability and by noncompliance, while the IV route may be too inconvenient, painful or Correspondence: Jay W Mason expensive for some patients, other modes of administration have been sought.11 Mason Cardiac Safety Consulting, 105 Londonderry Court, Reno, NV, 89511, USA Purpose of this report Tel +1 775 8499910 The purpose of this report is to review and assess the contribution of TD granisetron Fax +1 775 8499910 Email [email protected] to the control of acute and delayed CINV, and to delineate its place in the management submit your manuscript | www.dovepress.com Cancer Management and Research 2013:5 179–185 179 Dovepress © 2013 Mason and Moon, publisher and licensee Dove Medical Press Ltd. This is an Open Access article http://dx.doi.org/10.2147/CMAR.S34352 which permits unrestricted noncommercial use, provided the original work is properly cited. Powered by TCPDF (www.tcpdf.org) 1 / 1 Mason and Moon Dovepress of CINV. Because of the recent safety concerns related to QT (Cmax) is similar among young, elderly, and normal volunteers prolongation by 5-HT3 antagonists, leading to multiple label and patients, terminal elimination is considerably slower in changes12 and a product recall,13 the potential for arrhythmo- patients with cancer, and nearly as slow in elderly normals genesis through TD granisetron is discussed at length. compared to young normals (Table 1). Oral dosing with granisetron 2 mg qd (once a day) in Methods normal volunteers resulted in a mean Cmax of 5.5 nanogram/ 16 This report is based on a review of the medical literature, milliliter (ng/mL) and t1/2 of 7.9 hours on day 5, while a dose available US Food and Drug Administration (FDA) com- of 1 mg bid (twice a day) in patients with cancer resulted 16 munications and product labels, and a P&T Product Pro- in a Cmax of 5.9 ng/mL, according to the package insert. 14 filer provided by ProStrakan (Bridgewater, NJ, USA). In t1/2 in patients is not reported in the package insert or in the addition, pharmacokinetic and cardiac safety data regarding published literature. APF530, a sustained release subcutaneous (SC) preparation of granisetron, was provided by AP Pharma, Inc (Redwood Transdermal granisetron City, CA, USA). Product description The granisetron TD patch uses a drug-in-adhesive matrix Preparations, pharmacology, and diffusion method to deliver a predictable dose of granis- pharmacokinetics of granisetron etron for up to 7 days. The patch is a 52 cm2 rectangle that Currently available preparations contains 34.3 mg of granisetron, and delivers it at a rate of of granisetron 3.1 mg per 24 hours. Transdermal drug delivery is possible because the skin can absorb small, lipophilic molecules Granisetron is available as an oral tablet (1 mg or 2 mg), and by diffusion. The size of the transdermal patch, specific an IV infusion (1 mg in 1 mL and 3 mg in 3 mL ampules), characteristics of the matrix material in which the drug is both marketed under the brand name Kytril (Roche, Basel, For personal use only. suspended, properties of the drug itself, and the status of Switzerland) and as a generic compound. Granisetron in a TD the skin to which the patch is applied determine the rate patch (34.3 mg) was approved in 2008 and marketed under the and extent of drug delivery. While transdermal delivery is brand name Sancuso (ProStrakan, Inc). A sustained-release generally slow, requiring several hours or days to achieve SC injection (APF530, AP Pharma, Inc) may become avail- steady state, the plasma concentrations achieved are pre- able before or soon after publication of this report, as the US dictable and are not subject to rapid change, maximizing FDA has responded to a new drug application submission for the potential for efficacy without toxicities that result from this preparation, and approval during 2013 was established excessive plasma concentration. by the sponsor as its objective. Pharmacokinetics of transdermal Pharmacology of granisetron granisetron Granisetron and other selective 5-HT3 antagonists block Cancer Management and Research downloaded from https://www.dovepress.com/ by 54.70.40.11 on 17-Nov-2018 In a Phase 1 crossover study of twelve normal volunteers, receptors in afferent vagal nerve termini in the gut and in the Howell et al17 compared the pharmacokinetics of the 52 cm2 chemoreceptor trigger zone (CTZ). Vagal receptors in the gut, patch to that of oral granisetron 2 mg daily (Figure 1). when stimulated by serotonin release by the intestinal mucosa Several differences are evident. The time at which maximum as a result of chemotherapy, send a signal to the vomiting center and the CTZ that induces nausea and vomiting. Direct Table 1 Pharmacokinetics of granisetron stimulation of the CTZ by chemotherapeutic agents may also Health status Age, years Mean C Mean t induce emesis. Granisetron prohibits the emesis reflex by max 1/2 IV granisetron* blocking these receptors. Normal volunteers 21–42 64.3 ng/mL 4.91 hours 65–81 57.0 ng/mL 7.69 hours Patients with cancer 63.8 ng/mL 8.95 hours Pharmacokinetics of IV Oral granisetron and oral granisetron Normal volunteers† 5.5 ng/mL 7.9 hours As indicated in the package insert,15 the elimination half-life Patients with cancer‡ 5.9 ng/mL – Notes: *40 µg/kg; †2 mg qd; ‡1 mg bid. (t1/2) of IV granisetron (40 µg per kg) depends on both age Abbreviations: t1/2, elimination half-life; IV, intravenous; qd, once a day; bid, twice a and health status. While the maximum plasma concentration day; ng/mL, nanogram/milliliter; Cmax, maximum plasma concentration. 180 submit your manuscript | www.dovepress.com Cancer Management and Research 2013:5 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Dovepress Safety of granisetron preparations in cancer management 6 Patch 52 cm2 receiving a single dose (Straken Pharmaceutical Ltd, 2007) Mean concentration 5 patch 52 cm2:2.2 ng/ml of chemotherapy and repeated doses19 of chemotherapy over 2 mg oral 4 Mean concentration 3 to 5 days, in controlling both acute (first 24 hours) and oral:2.6 ng/ml 3 late (24–120 hours) CINV. In the single-day chemotherapy 2 18 1 study, 210 patients were randomized in a 1:1 ratio to receive Granisetron (ng/mL) 0 either oral granisetron or the TD patch, both administered 024287296 120 144 168 192 216 240 Time (hours) once. Total control of CINV (no nausea and no use of rescue medication) was achieved in 52.4% of patients in the former Figure 1 Plasma concentrations of granisetron resulting from repeated oral dosing (2 mg daily) and the Sancuso 52 cm2 TD patch17 in normal volunteers. and 43.7% in the latter group (not statistically or clinically Note: The patch was removed at the end of day 6 (144 hours). significantly different). Abbreviations: TD, transdermal; ng/mL, nanogram/milliliter. In the multiple-day study,19 in which 323 patients were randomized to receive daily oral granisetron given when plasma concentration was achieved (Tmax) was 1.5 hours to chemotherapy was administered, and 318 to receive the 2 hours during oral dosing, and approximately the same Cmax TD patch applied once 24 hours before chemotherapy and was achieved each day. Tmax for the patch was 48 hours, and removed on day 7, complete control of CINV (no more than Cmax varied substantially from day to day. While Cmax was mild nausea) was reported by 64.8% in the former group, greater after oral dosing compared to patch administration, and 60.2% in the latter (not significantly different) during the mean plasma concentration through 5 days was similar.
Load more

Recommended publications
  • In February 2013, Glaxosmithkline (GSK) Announced a Commitment To
    In February 2013, GlaxoSmithKline (GSK) announced a commitment to further clinical transparency through the public disclosure of GSK Clinical Study Reports (CSRs) on the GSK Clinical Study Register. The following guiding principles have been applied to the disclosure: Information will be excluded in order to protect the privacy of patients and all named persons associated with the study Patient data listings will be completely removed* to protect patient privacy. Anonymized data from each patient may be made available subject to an approved research proposal. For further information please see the Patient Level Data section of the GSK Clinical Study Register. Aggregate data will be included; with any direct reference to individual patients excluded *Complete removal of patient data listings may mean that page numbers are no longer consecutively numbered CONFIDENTIAL HM2009/00361/00HM2009/00361/00 TheThe GlaxoSmithKline GlaxoSmithKline group group of companies of companies NKP106254 Division: Worldwide Development Retention Category: GRS019 Information Type: Clinical Pharmacology Study Report Title: Randomised, double-blind, placebo controlled, cross-over study comparing the effects of both single dose and repeated dosing treatment for 14 days of vestipitant or vestipitant + paroxetine combination in an enriched population of subjects with tinnitus & hearing loss. Phase: II Compound Number: GW597599 Effective Date: 10-DEC-2009 Description: Tinnitus associated with hearing loss is a high prevalent audiologic disorder with important unmet needs as far as therapy is concerned. The present study explored the possible beneficial effects on tinnitus loudness or annoyance of a combination drug treatment aimed to increase the local inhibitory activity of neural circuitries involved in sound perception and generation.
    [Show full text]
  • ( 12 ) United States Patent
    US009974742B2 (12 ) United States Patent (10 ) Patent No. : US 9 , 974 , 742 B2 Ottoboni et al. (45 ) Date of Patent: * May 22, 2018 ( 54 ) EMULSION FORMULATIONS OF AN NK - 1 2013 /0236501 A1 * 9 /2013 Booth . .. .. .. A61K 9 /0019 424 / 400 RECEPTOR ANTAGONIST AND USES 2013 /0317016 AL 11 /2013 Hingorani et al. THEREOF 2016 / 0024092 Al 1 / 2016 Wan et al. 2016 / 0082013 Al 3 / 2016 Ottoboni et al . @(71 ) Applicant : Heron Therapeutics , Inc. , Redwood 2016 /0206622 A1 3 / 2016 Ottoboni et al . City , CA (US ) 2017 / 0112847 AL 4 /2017 Ottoboni et al. @(72 ) Inventors : Thomas B . Ottoboni, Belmont, CA (US ) ; Han Han , Mountain View , CA FOREIGN PATENT DOCUMENTS (US ) CN 102379 * 3 / 2012 CN 102379845 A 3 / 2012 @(73 ) Assignee : Heron Therapeutics, Inc. , San Diego , WO WO 2005 /016308 AL 2 / 2005 WO WO 2009 / 124756 AL 10 / 2009 CA (US ) WO WO 2011 / 158053 AL 12 / 2011 WO WO 2013 / 177501 A2 11 / 2013 @( * ) Notice : Subject to any disclaimer , the term of this WO WO 2014 /0209962 AL 12 /2014 patent is extended or adjusted under 35 WO WO 2014 /005606 AL 3 / 2016 U . S . C . 154 ( b ) by 0 days . days . WO WO 2016 /044784 Al 3 / 2016 This patent is subject to a terminal dis claimer . OTHER PUBLICATIONS (21 ) Appl. No. : 15 /012 , 532 Cassileth et al. in Arch . Intern Med . 1983 ; 143 ( 7 ) : 1347 - 1349 ( Abstract ) . * Dexamethasone Hydrogen Phosphate at web .archive . org/ web / ( 22 ) Filed : Feb . 1 , 2016 20141224130045 /http :/ /www . drugs . com / pro / dexamethasone -so dium -phosphate .html ( retrieved on the internet Mar.
    [Show full text]
  • CDR Clinical Review Report for Akynzeo
    CADTH COMMON DRUG REVIEW Clinical Review Report Netupitant/Palonosetron 300 mg/0.5 mg (Akynzeo) (Purdue Pharma) Indication: In combination with dexamethasone, once- per-cycle treatment for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy, or with moderately emetogenic cancer chemotherapy that is uncontrolled by a 5-hydroxytryptamine-3 receptor antagonist alone. Service Line: CADTH Common Drug Review Version: Final Publication Date: June 2018 Report Length: 96 Pages Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9.446,029 B2 Boscan Et Al
    USOO9446O29B2 (12) United States Patent (10) Patent No.: US 9.446,029 B2 BOScan et al. (45) Date of Patent: Sep. 20, 2016 (54) USE OF NK-1 RECEPTOR ANTAGONISTS IN GB 2216529 10, 1989 MANAGEMENT OF VISCERAL PAIN WO 9102745 A1 3, 1991 WO 911226.6 A1 8, 1991 (75) Inventors: Pedro Boscan, Bellvue, CO (US); WO O11801.6 A1 3, 2001 David Twedt, Fort Collins, CO (US) OTHER PUBLICATIONS (73) Assignee: Colorado State University Research Glerum et al. (Veterinary Surgery, 30, 351-358, 2001).* Foundation, Fort Collins, CO (US) Devitt et al. (JAVMA, 227, 6, Sep. 15, 2005).* Papich (Veterinary Pharmacology and Therapeutics, Ninth Edition, (*) Notice: Subject to any disclaimer, the term of this 2009, p. 1247-1272, editors: Jim E. Riviere Mark G. Papich).* patent is extended or adjusted under 35 Bradesi et al. (Gastroenterology, 2006, 130, 1729-1742).* U.S.C. 154(b) by 452 days. Heard, D.J. et al. Effect of acepromazine on the anesthetic require ment of halothane in the dog, AJVR, 1986, pp. 2113-2115, vol. 47. (21) Appl. No.: 13/192.283 No. 10. Hellyer, P.W. et al. Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a (22) Filed: Jul. 27, 2011 combination of isoflurane and fentanyl, AJVR, 2001, pp. 555-560, (65) Prior Publication Data vol. 62, No. 4. Muir, W.W. III, et al. Effects of morphine, lidocaine, ketamine, and US 2012/002898O A1 Feb. 2, 2012 morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane, AJVR, Related U.S.
    [Show full text]
  • Use and Cardiovascular Safety of Transdermal and Other Granisetron Preparations in Cancer Management
    Cancer Management and Research Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management 1 Jay W Mason Abstract: 5-HT3 antagonists have been available as oral and intravenous preparations for Thomas E Moon2 decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and 1School of Medicine, University of Utah, Salt Lake City, UT, these preparations have been shown to have less potential to prolong QT than other drugs in 2Tarizona eHealth Services, Inc, the class. Emeryville, CA, USA Keywords: chemotherapy-induced nausea, vomiting, granisetron, QT prolongation Introduction Problem of chemotherapy-induced nausea and vomiting For personal use only. Chemotherapy-induced nausea and vomiting (CINV) occurs in 10%–90% of patients, depending on the emetic risk of the chemotherapeutic agent.1,2 There is a consider- able cost involved, not only for the expense of hospitalization and the direct treatment of CINV, but also because of the loss of workdays and the consequences of delayed 3–7 chemotherapy administration. There is consistent evidence that 5-HT3 antagonist antiemetic therapy has improved this problem without increasing the cost.3–7 Unmet needs in CINV treatment Delayed nausea and vomiting occurring hours or days after chemotherapy, either as a result of reduced plasma concentrations
    [Show full text]
  • Management of Chemotherapy-Induced Nausea and Vomiting
    R E V I E W A R T I C L E Management of Chemotherapy-Induced Nausea and Vomiting POOJA D EWAN, SWATI SINGHAL* AND DEEPIKA HARIT From Department of Pediatrics, UCMS and GTB Hospital, Delhi 110 095; and *Department of Pediatrics, Maulana Azad Medical College, Delhi 110 001; India. Correspondence to: Dr Pooja Dewan, DII/65, Kaka Nagar, Dr Zakir Hussain Marg, New Delhi 110 003, India. [email protected] Context: Chemotherapy-induced nausea and vomiting (CINV) is a significant problem in the treatment of children with cancer. The last decade has seen a variety of newer antiemetics being evaluated for CINV; their efficacy and side-effects need to be assessed in children. This article attempts to highlight this revised management of CINV. Evidence acquisition: Online search; journals. Search period: 6 months. Results: Newer drugs (aprepitant, fosapritant and newer 5HT3 antagonists) have been found to be effective in CINV: both acute and delayed phases. Most of the available literature is, however, based on adult oncology patients, with a few trials on adolescent patients. Conclusion: Every child receiving treatment for cancer should be evaluated for possible CINV. Their treatment should take into account the emetogenic potential of the chemotherapeutic drugs. Newer antiemetic drugs have good efficacy and can be tried in pediatric patients, especially in children > 11 years of age. Keywords: Antiemetics, Cancer, Chemotherapy, Nausea, Vomiting. hemotherapy is a common modality tears, and anxiety, it is imperative to provide for treatment of cancer. Regardless prophylaxis and treatment for CINV. of the fact that chemotherapy improves CLASSIFICATION Csurvival; it has its own toxicity and side- effects, which have a negative impact on the quality Chemotherapy-induced nausea and vomiting of life of children with cancer.
    [Show full text]
  • Guideline for the Prevention of Acute Nausea and Vomiting Due to Antineoplastic Medication in Pediatric Cancer Patients
    Guideline for the Prevention of Acute Nausea and Vomiting due to Antineoplastic Medication in Pediatric Cancer Patients The POGO Antineoplastic–induced Nausea and Vomiting Guideline Development Panel: L. Lee Dupuis MScPhm, ACPR, FCSHP Sabrina Boodhan BScPhm, ACPR Mark Holdsworth PharmD, BCOP Paula D. Robinson MD, MSc Richard Hain MD Carol Portwine MD, FRCPC, PhD Erin O’Shaughnessy RN, MScN, CPHON Lillian Sung MD, PhD Recommended citation: Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, O’Shaughnessy E and Sung L. Guideline for the Prevention of Acute Nausea and Vomiting due to Antineoplastic Medication in Pediatric Cancer Patients. Pediatric Oncology Group of Ontario; Toronto. 2012. 1 Version date: February 28, 2013 The Pediatric Oncology Group of Ontario (POGO) Guideline for the Prevention of Acute Nausea and Vomiting due to Antineoplastic Medication in Pediatric Cancer Patients was developed by health care professionals using evidence-based or best practice references available at the time of its creation. The content of the guideline will change since it will be reviewed and revised on a periodic basis. Care has been taken to ensure accuracy of the information. However, every health care professional using this guideline is responsible for providing care according to their best professional judgement and the policies and standards in place at their own institution. OVERVIEW OF MATERIAL Guideline release date: August, 2012 Status: Adapted, revised and updated Sources: Print copies available through the POGO office:
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0231688 A1
    US 20190231688A1 ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0231688 A1 Ottoboni et al. (43 ) Pub. Date : Aug. 1 , 2019 ( 54 ) METHOD OF ADMINISTERING EMULSION A61K 9 / 00 ( 2006 .01 ) FORMULATIONS OF AN NK - 1 RECEPTOR A61K 47 / 24 (2006 .01 ) ANTAGONIST A61K 31/ 573 (2006 . 01 ) A61K 47 /44 ( 2006 .01 ) (71 ) Applicant: Heron Therapeutics , Inc . , San Diego , A61K 47/ 10 ( 2006 .01 ) CA (US ) A61K 47 / 12 ( 2006 . 01 ) A61K 47 / 26 ( 2006 . 01 ) ( 72 ) Inventors : Thomas B . Ottoboni, Belmont, CA A61K 31/ 496 ( 2006 .01 ) ( US ) ; Barry D . Quart, Las Vegas, NV (52 ) U . S . CI. (US ) CPC .. .. .. A61K 9 / 107 ( 2013 . 01 ) ; A61K 31/ 5377 ( 2013 .01 ) ; A61K 9 /0019 ( 2013 . 01 ) ; A61K ( 21 ) Appl. No .: 16 / 261, 459 47 / 24 ( 2013 .01 ) ; A61K 31 /496 ( 2013 .01 ) ; A61K 47/ 44 ( 2013 .01 ) ; A61K 47 /10 (2013 .01 ) ; (22 ) Filed : Jan . 29 , 2019 A61K 47 /12 ( 2013 .01 ) ; A61K 47 /26 ( 2013 .01 ) ; Related U . S . Application Data A61K 31/ 573 (2013 .01 ) ( 60 ) Provisional application No . 62/ 624 , 050 , filed on Jan . 30 , 2018 . (57 ) ABSTRACT Publication Classification ( 51 ) Int. Ci. Disclosed herein are methods of administering pharmaceu A61K 9 / 107 ( 2006 .01 ) tical formulations of a neurokinin - 1 (NK - 1 ) receptor antago A61K 31/ 5377 ( 2006 . 01 ) nist to a subject in need of treatment of emesis . Patent Application Publication Aug. 1 , 2019 Sheet 1 of 4 US 2019/ 0231688 A1 Ayyyyy . * L-9.21um SSS * 44 FIG.1B FIG.1D . S MXXS .91umL-2 FIG.1A FIG.1C * : * :: : : 00 28 PO20.
    [Show full text]
  • Gsk-101287-Synopsis-Redact
    CONFIDENTIALCONFIDENTIAL HM2005/00235/00HM2005/00235/00 NKO101287NKO101287 Synopsis Identifier: HM2005/00235/00 Study Number: NKO101287 Title: A Multicenter, Randomized, Double-blind, Double-Dummy, Placebo-controlled, Parallel Group, Phase II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Oral (25mg) and Intravenous (3mg and 18mg) Formulations of the Neurokinin-1 Receptor Antagonist, GW597599, When Administered with Intravenous Ondansetron Hydrochloride for the Prevention of Post-Operative Nausea and Vomiting (PONV) and Post-Discharge Nausea and Vomiting (PDNV) in Female Subjects with Known Risk Factors for PONV Who are Undergoing Surgical Procedures Associated with an Increased Emetogenic Risk Investigator(s): This was a multicenter study. Study center(s): A total of 49 centers randomized subjects for this study: 13 in the US, seven in Canada, six in Australia, four each in Belgium and the Czech Republic, three each in Poland and the Netherlands, two each in the UK, Finland, Chile, and South Africa, and one in Turkey. Publication(s): None at the time of this report. Study Period: 21 December 2004 to 21 April 2006. Phase of Development: II Objectives: The primary objective of this study was to determine whether a single oral or IV dose of vestipitant, when administered in combination with IV ondansetron hydrochloride, improves the prophylaxis against emesis (defined as vomiting or retching) during the first 24 hrs following emergence from anesthesia in female subjects with known risk factors for post-operative nausea and vomiting (PONV) who were undergoing surgical procedures associated with increased emetogenic risk. The secondary objectives of this study were: • To determine, within this study population, whether a single dose of oral or IV vestipitant in combination with intravenous ondansetron hydrochloride: • Improves the prophylaxis against emesis measured daily for up to 120 hrs following the emergence from anesthesia.
    [Show full text]
  • Neurokinin-1 Receptor Antagonists in Preventing Postoperative Nausea and Vomiting a Systematic Review and Meta-Analysis
    Neurokinin-1 Receptor Antagonists in Preventing Postoperative Nausea and Vomiting A Systematic Review and Meta-Analysis Meng Liu, MD, Hao Zhang, MD, PhD, Bo-Xiang Du, MD, PhD, Feng-Ying Xu, MD, Zui Zou, MD, PhD, Bo Sui, MD, and Xue-Yin Shi, MD Abstract: Newly developed neurokinin-1 receptor (NK-1R) Limited data suggested that NK-1R antagonists, especially aprepi- antagonists have been recently tried in the prevention of postoperative tant were effective in preventing PONV compared with placebo. More nausea and vomiting (PONV). This systematic review and meta- large-sampled high-quality RCTs are needed. analysis was conducted to explore whether NK-1R antagonists were (Medicine 94(19):e762) effective in preventing PONV. The PRISMA statement guidelines were followed. Randomized Abbreviations: ASA = American Society of Anesthesiologists, CR clinical trials (RCTs) that tested the preventive effects of NK-1R = complete response, HEC = highly emetogenic chemotherapy, ITT antagonists on PONV were identified by searching EMBASE, = intention to treat, MEC = moderately emetogenic chemotherapy, CINAHL, PubMed, and the Cochrane Library databases followed by NK-1R = neurokinin-1 receptor, NMA = network meta-analysis, screening. Data extraction was performed using a predefined form and NST = nucleus of solitary tract, PCA = patient-controlled trial quality was assessed using a modified Jadad scale. The primary analgesia, PONV = postoperative nausea and vomiting, RCTs = outcome measure was the incidence of PONV. Meta-analysis was randomized clinical trials. performed for studies using similar interventions. Network meta- analysis (NMA) was conducted to compare the anti-vomiting effects of placebo, ondansetron, and aprepitant at different doses. INTRODUCTION Fourteen RCTs were included.
    [Show full text]
  • Neurokinin1 Antagonists Potentiate Antidepressant Properties Of
    Neuropsychopharmacology (2009) 34, 1039–1056 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org Neurokinin1 Antagonists Potentiate Antidepressant Properties of Serotonin Reuptake Inhibitors, Yet Blunt Their Anxiogenic Actions: A Neurochemical, Electrophysiological, and Behavioral Characterization 1 1 1 1 ¨ 1 Alain Gobert , Mauricette Brocco , Anne Dekeyne , Benjamin Di Cara , Gaelle Bouchez , Franc¸oise Lejeune1, Robert L Gannon2 and Mark J Millan*,1 1 2 Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, Paris, France; Department of Biology, Valdosta State University, Valdosta, GA, USA Though neurokinin (NK ) receptor antagonists are active in experimental models of depression, clinical efficacy has proven 1 1 disappointing. This encourages interest in association of NK receptor blockade with inhibition of serotonin (5-HT) reuptake. The 1 selective NK1 antagonist, GR205171, dose-dependently enhanced citalopram-induced elevations of extracellular levels of 5-HT in frontal cortex, an action expressed stereospecifically vs its less active distomer, GR226206. Further, increases in 5-HT levels in dorsal hippocampus, basolateral amygdala, nucleus accumbens, and striatum were likewise potentiated, and GR205171 similarly facilitated the influence of fluoxetine upon levels of 5-HT, as well as dopamine and noradrenaline. In parallel electrophysiological studies, the inhibitory influence of citalopram and fluoxetine upon raphe-localized serotonergic neurones was stereospecifically blunted by GR205171. Antidepressant actions of citalopram in a forced-swim test in mice were stereospecifically potentiated by GR205171, and it also enhanced attenuation by citalopram of stress-related ultrasonic vocalizations in rats. Further, GR205171 and citalopram additively abrogated the advance in circadian rhythms provoked by exposure to light in hamsters.
    [Show full text]
  • Tachykinin Receptors (Version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
    IUPHAR/BPS Guide to Pharmacology CITE https://doi.org/10.2218/gtopdb/F62/2019.4 Tachykinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database Jeffrey Barrett1, Brenden Canning2, Joseph Coulson3, Erin Dombrowsky1, Steven D. Douglas4, Tung M. Fong5, Christa Y. Heyward1, Susan E. Leeman6 and Pranela Remeshwar7 1. Children's Hospital of Philadelphia, USA 2. Johns Hopkins, USA 3. University of Edinburgh, UK 4. University of Pennsylvania, USA 5. Covance Inc, USA 6. Boston University, USA 7. University of Medicine and Dentistry of New Jersey, USA Abstract Tachykinin receptors (provisional nomenclature as recommended by NC-IUPHAR [90]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin α, neuromedin L), neurokinin B (NKB; previously known as neurokinin β, neuromedin K),n europeptide K and neuropeptide γ (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in in vitro pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy. Contents This is a citation summary for Tachykinin receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers.
    [Show full text]