DOCSLIB.ORG

Pdf/Poison-Issue-Brief.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pdf/Poison-Issue-Brief.Pdf Advisory Committee Briefing Materials: Available for Public Release Joint Meeting of the Anesthetic and Analgesic Drug Products and the Drug Safety and Risk Management Advisory Committees October 5, 2016 kaleo, Inc. Briefing Dossier Advisory Committee Briefing Materials: Available for Public Release TABLE OF CONTENTS LIST OF FIGURES .........................................................................................................................3 LIST OF TABLES ...........................................................................................................................4 LIST OF ABBREVIATIONS ..........................................................................................................5 LIST OF APPENDICIES ................................................................................................................6 1. EXECUTIVE SUMMARY ......................................................................................................7 2. BACKGROUND ....................................................................................................................11 2.1. Opioid Overdose Epidemic ...........................................................................................11 2.2. Naloxone Products Used in Medical Settings ...............................................................12 2.3. Naloxone HCl Products Used in the Community Setting .............................................14 3. SCIENTIFIC BACKGROUND..............................................................................................19 3.1. Naloxone HCl and EVZIO Safety ................................................................................19 3.1.1. Literature Review of Naloxone HCl Safety ......................................................19 3.1.2. EVZIO Post-Marketing Safety Surveillance .....................................................20 3.2. Preclinical Pharmacokinetics ........................................................................................21 3.2.1. Absorption .........................................................................................................21 3.2.2. Distribution .......................................................................................................23 3.2.3. Metabolism (Interspecies Comparison) ............................................................24 3.2.4. Excretion ...........................................................................................................24 3.3. Clinical Pharmacokinetics and Pharmacodynamics......................................................25 3.3.1. Pharmacokinetics of Intravenous Administration of Naloxone HCl ................25 3.3.2. Pharmacokinetics of Naloxone HCl Administered Intramuscular/Subcutaneous .............................................................................27 3.3.3. Pharmacokinetics of Naloxone HCl Administered Via the Intranasal Route .................................................................................................................29 3.3.4. Pharmacodynamics - Published Literature........................................................36 3.4. Data to Support the Device Constituent Component of Naloxone Delivery Products Intended for Use in the Community Setting ...........................................38 3.4.1. EVZIO Product Characteristics.........................................................................39 3.4.2. EVZIO Sharps Injury Prevention Feature .........................................................41 3.4.3. EVZIO Features that Aid the User after Administering a Dose .......................41 3.4.4. In vitro Performance Testing of EVZIO for “Real Word” Use ........................41 3.4.5. Human Factors Studies for EVZIO ...................................................................42 4. DISCUSSION AND CONCLUSIONS ..................................................................................44 5. REFERENCES .......................................................................................................................47 2 1 September 2016 Advisory Committee Briefing Materials: Available for Public Release LIST OF FIGURES Figure 1. Serum and Brain Concentrations of Naloxone in the Rat after Intravenous Administration ............................................................................................................22 Figure 2. Pharmacokinetic Profile of Morphine and Naloxone in the Rat .................................23 Figure 3. Naloxone Plasma Concentration-Time Profiles Following Intravenous Administration of 2 mg Naloxone HCl ......................................................................26 Figure 4. Naloxone Plasma Concentration-Time Profiles Following Intravenous Administration of 0.035 mg/kg Naloxone HCl ..........................................................27 Figure 5. Mean (±SD) Naloxone Plasma Concentration-Time Profiles Following Intramuscular/Subcutaneous Administration of 0.4 mg Naloxone HCl .....................28 Figure 6. Naloxone Plasma Concentration-Time Profiles Following IN Administration of 20 mg Naloxone HCl Powder ................................................................................30 Figure 7. Mean Naloxone Plasma Concentration-Time Profiles Following Intranasal Administration of Naloxone HCl (NARCAN Nasal Spray) .......................................31 Figure 8. Mean (±SD) Naloxone Plasma Concentration-Time Profiles of 2.0 mg Naloxone HCl Administered Using an Intranasal Naloxone Kit and Intramuscular Using a Standard Syringe ....................................................................33 Figure 9. Mean (±SD) Naloxone Plasma Concentration-Time Profiles following Intranasal Administration of 2.0 mg Naloxone with and without Vasoconstrictor Pre-treatment, (A) 0-6 hour and (B) 0-1 hour ..................................35 Figure 10. The Effects of (A) Placebo, (B) 0.2 mg Naloxone HCl, and (C) 0.4 mg Naloxone HCl, 30 Minutes after Administration of Morphine ..................................36 Figure 11. The Effects of (A) Placebo, (B) 0.025 mg Naloxone HCl, (C) 0.1 mg Naloxone HCl, and (D) 0.4 mg Naloxone HCl, 55 Minutes after Administration of Morphine-6-Glucuronide ..............................................................37 Figure 12. The Effects of Placebo, 1 mg Naloxone HCl, 5 mg Naloxone HCl, and 10 mg Naloxone HCl after Intravenous Administration of Buprenorphine ....................38 Figure 13. Illustration of EVZIO, EVZIO Outer Case, and a Used EVZIO ................................40 Figure 14. Illustration of a Trainer for EVZIO ............................................................................41 3 1 September 2016 Advisory Committee Briefing Materials: Available for Public Release LIST OF TABLES Table 1. Naloxone HCl Products Currently Used in the Out of Hospital Setting ....................15 Table 2. United States Distribution Information for EVZIO ....................................................21 Table 3. Spontaneous Adverse Event Reports for EVZIO .......................................................21 Table 4. Summary of Naloxone Plasma Pharmacokinetic Parameters and Comparative Bioavailability Results (Study IJ-900DV-03O) ....................................29 Table 5. Comparison of Intranasal 2.0 mg Naloxone HCl Pharmacokinetics in Subjects with Chronic Rhinitis with and without Concomitant Nasal Vasoconstrictor Use ....................................................................................................35 Table 6. Summary of Successful Critical Task Completion in Two Controlled Usability Studies .........................................................................................................43 4 1 September 2016 Advisory Committee Briefing Materials: Available for Public Release LIST OF ABBREVIATIONS Abbreviation Term ASTM American Society for Testing and Materials AUC0-t area under the concentration-time curve from baseline to the last measurable concentration AUC0-inf area under the concentration-time curve from baseline extrapolated to infinity AUC0-Tmax area under the curve from time zero to the Tmax for each subject in the 2.0 mg IN study arm Cmax maximum plasma concentration CI Confidence Interval CNS central nervous system FDA Food and Drug Administration g%CV geometric percent coefficient of variation HCl hydrochloride salt hr hours IFU instructions for use IEC International Electrotechnical Commission IN intranasal(ly) IM Intramuscular(ly) ISO International Organization for Standardization ISTA International Safe Transit Association IV intravenous(ly) M6G morphine-6-glucuronide MedDRA Medical Dictionary for Regulatory Activities min minutes NDA new drug application PK pharmacokinetics PIL patient information leaflet SC subcutaneous(ly) SD standard deviation T1/2 terminal-phase elimination half-life Tmax time at maximum plasma concentration UL Underwriter Laboratories USP United States Pharmacopeia 5 1 September 2016 Advisory Committee Briefing Materials: Available for Public Release LIST OF APPENDICIES Appendix 1: EVZIO (naloxone HCl injection) Auto-Injector: Prescribing Information April 2014 Appendix 2: EVZIO (naloxone HCl injection) Auto-Injector: Patient Information / Instructions for Use April 2014 Appendix 3: Trainer for EVZIO: Trainer Instructions for Use April 2014 Appendix 4: Opioid Emergencies and Life-Threatening Respiratory Depression: Kaleo, Inc. 2016 6 1 September 2016 Advisory Committee Briefing Materials: Available for Public Release 1. EXECUTIVE SUMMARY The
Load more

Recommended publications
  • HIV-1 Protease Inhibitory Activity of Amprenavir –Poly(Ethylene Glycol)
    ©2014 Mahta Samizadeh ALL RIGHTS RESERVED ANTI-HIV DRUG CONJUGATES FOR ENHANCED MUCOSAL PRE-EXPOSURE PROPHYLAXIS By MAHTA SAMIZADEH A dissertation submitted to the Graduate School-New Brunswick Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Doctor of Philosophy Graduate Program in Pharmaceutical Science Written under the direction of Professor Patrick J. Sinko And approved by ____________________________ ____________________________ ____________________________ ____________________________ New Brunswick, New Jersey May, 2014 ABSTRACT OF THE DISSERTATION ANTI-HIV DRUG CONJUGATES FOR ENHANCED MUCOSAL PRE-EXPOSURE PROPHYLAXIS By Mahta Samizadeh Dissertation Director: Professor Patrick J. Sinko To combat HIV pandemic, targeting HIV mucosal transmission appears to be more effective than targeting later stages of the infection owing to the viral vulnerability and higher efficacy of antiretrovirals at this very early stage of HIV infection. The objective of the current project is to investigate the complementary benefits of combining an anti-HIV drug (amprenavir, APV), a cell-penetrating peptide (bactenicin 7, Bac7 CPP) and poly (ethylene glycol) (PEG) together as a nanocarrier conjugate for fast and efficient cytosolic delivery of the drug. The nanocarrier is to be incorporated into an alcohol-free thermosensitive foam for colonic/rectal delivery. In the initial studies, APV-PEG conjugates were prepared using 2 to 30 kDa PEGs and protease inhibition properties were assessed in buffer using FRET-based protease inhibition assay. The results suggested that PEG size between 2 and 5 kDa is the optimum range for maintaining the protease inhibition activity. For further studies, APV- PEG3.4-FITC (APF) and a PEGylated APV conjugated with Bac7 CPP (APV-PEG3.4- Bac7 CPP; APB) were prepared.
    [Show full text]
  • WO 2008/025791 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date PCT 6 March 2008 (06.03.2008) WO 2008/025791 Al (51) International Patent Classification: [US/US]; 25 Windrose Way, Greenwich, CT 06830 (US). A61K 31/485 (2006.01) A61K 9/20 (2006.01) WALDEN, Malcolm [GB/GB]; c/o Mundipharma R e A61P 25/04 (2006.01) A61K 9/70 (2006.01) search Limited, Cambridge Science Park, Milton Road, Cambridge CB4 OGW (GB). (21) International Application Number: PCT/EP2007/058978 (74) Agent: BUEHLER, Dirk; Elisenhof, Elisenstrasse 3, 80335 Munchen (DE). (22) International Filing Date: 29 August 2007 (29.08.2007) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, (26) Publication Language: English CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, (30) Priority Data: IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, 061 19839.6 30 August 2006 (30.08.2006) EP LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, (71) Applicant (for all designated States except US): EURO- PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, CELTIQUE S.A. [LU/LU]; 122, Boulevard de laPetrusse, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, L-2330 Luxembourg (LU).
    [Show full text]
  • United States Patent (10) Patent No.: US 8.236,957 B2 Rezaie Et Al
    US008236957B2 (12) United States Patent (10) Patent No.: US 8.236,957 B2 Rezaie et al. (45) Date of Patent: Aug. 7, 2012 (54) PROCESS FOR MAKING FOREIGN PATENT DOCUMENTS MORPHINAN-6O-OLS WO WO 2007/121114 10/2007 WO WO 2008,137672 11, 2008 (75) Inventors: Robert Rezaie, Blackstone Heights OTHER PUBLICATIONS (AU); Timothy S. Bailey, Blackstone Heights (AU) International Search Report PCT/AU2009/000925, Aug. 19, 2009. Sargent, et al “Hydroxylated Codeine Derivatives”, Journal of (73) Assignee: Janssen Pharmaceutica B.V. (BG) Sir "S.R.E.E.Eine, Journal of - r Organic Chemistry, 1960, pp. 773-781. (*) Notice: Subject to any disclaimer, the term of this Burke, et al., “Probes for Narcotic Receptor Mediated Phenomena. patent is extended or adjusted under 35 11. Synthesis of 17-Methyl- and 17-Cyclopropylmethyl-3, U.S.C. 154(b) by 437 days. 14-Dihydroxy-4.5o-Epoxy-6B-Fluoromorphinans (FOXY and CYCLOFOXY) as models of Opioid Ligands suitable for Positron (21) Appl. No.: 12/538,545 Emission Transaxial Tomography.” Heterocycles, vol. 23, 1985, pp. 99-106. 22) Filed: Aug. 10, 2009 Brine, et al., “Ring C Conformation of 6B-Naltrexol and (22) g. U, 6O-Naltrexol. Evidence from Proton and Carbon-13 Nuclear Mag (65) Prior PublicationO O Data tic Resonance" Journal of Organic Chemistry, vol. 41, No. 21 1976, pp. 3445-3448. US 201O/OO36128A1 Feb. 11, 2010 Olsen, et al., “Conjugate Addition Ligands of Opioid Antagonists. Methacrylate Esters and Ethers of 60- and 6B-Naltrexol'. J. Med. Related U.S. Application Data Chem., 1990, vol. 33, pp. 737-741.
    [Show full text]
  • Potential Applications and Human Biosafety of Nanomaterials Used in Nanomedicine
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Appl Toxicol Manuscript Author . Author manuscript; Manuscript Author available in PMC 2019 May 09. Published in final edited form as: J Appl Toxicol. 2018 January ; 38(1): 3–24. doi:10.1002/jat.3476. Potential applications and human biosafety of nanomaterials used in nanomedicine Hong Sua,†, Yafei Wanga,†, Yuanliang Gua,†, Linda Bowmanb, Jinshun Zhaoa,b,*, and Min Dingb,* aDepartment of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province 315211, People’s Republic of China bToxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA Abstract With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical
    [Show full text]
  • NIDA Drug Supply Program Catalog, 25Th Edition
    RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION 6α-Naloxol Item No. 22146 CAS Registry No.: 20410-95-1 N Formal Name: (5α,6α)-4,5-epoxy-17-(2-propen- 1-yl)-morphinan-3,6,14-triol OH Synonyms: 6-hydroxy Naloxone, NLL MF: C19H23NO4 FW: 329.4 Purity: ≥98% Supplied as: A crystalline solid HO O H OH Storage: -20°C Stability: ≥5 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Description 6α-Naloxol (Item No. 22146) is an analytical reference material categorized as an opioid. It is an active metabolite of naloxone (Item No. ISO60191 | 15594) that has approximately the same binding affinity as naloxone for µ- and δ-opioid receptors.1 This product is intended for research and forensic applications. This product is qualified as a Reference Material that has been manufactured and tested to ISO/IEC 17025 and ISO 17034 international standards. Reference 1. Wang, D., Raehal, K.M., Bilsky, E.J., et al. Inverse agonists and neutral antagonists at µ opioid receptor (MOR): Possible role of basal receptor signaling in narcotic dependence. J. Neurochem. 77(6), 1590-1600 (2001). WARNING CAYMAN CHEMICAL THIS PRODUCT IS FOR RESEARCH ONLY - NOT FOR HUMAN OR VETERINARY DIAGNOSTIC OR THERAPEUTIC USE. 1180 EAST ELLSWORTH RD SAFETY DATA ANN ARBOR, MI 48108 · USA This material should be considered hazardous until further information becomes available. Do not ingest, inhale, get in eyes, on skin, or on clothing. Wash thoroughly after handling. Before use, the user must review the complete Safety Data Sheet, which has been sent via email to your institution.
    [Show full text]
  • Oral PEG-Naloxol) Presented at American Academy of Pain Management Meeting
    September 26, 2007 Positive Results for NKTR-118 (oral PEG-naloxol) Presented at American Academy of Pain Management Meeting NKTR-118 Currently in Phase 1 Clinical Development for the Treatment of Opioid Bowel Dysfunction SAN CARLOS, Calif., Sept 26, 2007 /PRNewswire-FirstCall via COMTEX News Network/ -- Nektar Therapeutics (Nasdaq: NKTR) presented positive results this week from Phase 1 and preclinical studies of NKTR-118 (oral PEG-naloxol) at the American Academy of Pain Management (AAPM) meeting in Las Vegas, Nevada. NKTR-118 is Nektar's proprietary oral therapy being studied for its potential to treat patients suffering from opioid-bowel dysfunction (OBD), including opioid-induced constipation (OIC). Data from a single-dose, proof-of-principle Phase 1 trial on NKTR-118 demonstrate that the drug antagonized the morphine- induced delay in gastrointestinal (GI) transit time without reversing the central opioid effect as measured by pupillometry. Further, the study shows that the drug was well-tolerated at single, oral doses up to 1,000 mg. Data from this study were also presented earlier this month at the American College of Clinical Pharmacology meeting in San Francisco, California. In preclinical studies presented at AAPM this week, oral NKTR-118 improved GI transit time in an animal model of morphine- induced constipation, while maintaining a substantial analgesic effect. In addition, NKTR-118 demonstrated significantly lower brain permeation than naloxone. "These positive study results for NKTR-118 show that the drug offers potential for treating opioid-induced constipation, a serious and debilitating side effect of opioid therapy," said Tim Riley, Ph.D. Vice President of PEGylation Research at Nektar.
    [Show full text]
  • Phylogenetic Distribution of the Hepatic Enzyme System for Reducing Naloxone to 6~- and 6/%Naloxol in Vertebrates
    Comp. Biochem. Phv.siol. Vol. 65C, pp. 93 to 97 0306-4492/80/0401-0093502.00/0 © Pergamon Press Ltd 1980, Printed in Great Britain PHYLOGENETIC DISTRIBUTION OF THE HEPATIC ENZYME SYSTEM FOR REDUCING NALOXONE TO 6~- AND 6/%NALOXOL IN VERTEBRATES S. C. ROERIG, K. L. CHRISTIANSEN,M. A. JANSEN, R. I. H. WANG, J. M. FUJIMOTO and M. NICVd~RSON Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226; Toxicology Research Laboratories, Wood Veterans Administration Center, Wood, WI 53193; and Milwaukee Public Museum, Milwaukee, WI 53203, U.S.A. (Received 21 August 1979) Abstrac~l. Livers from a variety of vertebrate species were examined for reduction of naloxone to 6~- and 6/~-naloxol. 2. Bird and reptile livers possessed relatively high rates of enzyme activity and formed predominantly 6c¢-naloxol. 3. Livers from fish and amphibia showed generally low rates of naloxone reduction and more equal amounts of 6~- and 6/3-naloxol. 4. Naloxone reduction in mammal livers was intermediate in activity and resulted primarily in 6/3-naloxol even though guinea pigs were a particularly interesting exception. 5. It was not possible to relate product stereoselectivity to phylogenetic development. INTRODUCTION Naloxone hydrochloride was provided by Endo Labora- tories, Garden City, NY. Standard 6a-naloxol and The status of the cytoplasmic aldo-keto reductases as 6fl-naloxol hydrochloride salts were obtained from the a class of drug metabolizing enzymes was reviewed by National Institute on Drug Abuse (NIDA). Glucose-6- Baucher (1976). Among them are enzymes which phosphate (G6P), glucose-6-phosphate dehydrogenase metabolize warfarin, daunorubicin, cyclohexanone (G6PD) and NADP + were purchased from Sigma Chemi- and naloxone, These enzyme systems have been found cal Company, St.
    [Show full text]
  • Consumption of Movantik™ (Naloxegol) Results in Detection Of
    Clinical Biochemistry 67 (2019) 48–53 Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem Consumption of Movantik™ (Naloxegol) results in detection of naloxone in the patient's urine evaluated by confirmatory urine drug testing T ⁎ Mehran Haidari , Sravan Mansani, Dezaray Ponds, Lissett Romero, Saad Alsaab Elite Medical Laboratory Solutions, Tomball, TX, United States of America ABSTRACT Background: Many patients on chronic opioid therapy suffer from constipation, one of the most common side effect of opioids. Movantik™ (naloxegol) is an opioid antagonist that is recently introduced in the market to treat opioid-induced constipation and contains naloxegol as the active ingredient. Naloxegol is a pegylated (polyethylene glycol-modified) derivative of α-naloxol. Detection of naloxone in the patients urine after consumption of naloxegol was not reported by the manufacturer and may mislead the prescribing clinicians. This study was conducted to investigate the presence of naloxone in the urine of patients that consume movnatik in pain management clinics. Methods: The presence of naloxone and naloxol in the urine of 45 patients that consumed naloxegol and 25 patients that consumed suboxone™ were investigated using a liquid chromatography mass spectrometry (LCMS) method. The urinary concentration of naloxone, naloxol, and their glucuronide conjugates were evaluated in five volunteers that took one pill of naloxegol for one day and one volunteer who took the pill for three days. Results: Naloxone was detected in the urine of 45 individuals that were prescribed naloxegol. Urinary concentration of naloxone showed a distribution with a mean of 25 ± 18 ng/ml. Consumption of one pill of 25 mg naloxegol resulted in the detection of naloxol and naloxone in the urine of 5 volunteers 1 h after taking the pill.
    [Show full text]
  • Download Thesis
    This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Non-Injectable Naloxone for the Prevention of Opioid Overdose Deaths McDonald, Rebecca Silvia Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 25. Sep. 2021 NON-INJECTABLE NALOXONE FOR THE PREVENTION OF OPIOID OVERDOSE DEATHS Rebecca McDonald Addictions Department Institute of Psychiatry, Psychology and Neuroscience Thesis submitted to King’s College London for the degree of Doctor of Philosophy (PhD) May 2017 1 2 Abstract Background and Aims: Naloxone is the standard treatment for reversal of opioid overdoses.
    [Show full text]
  • Opioid Receptor
    Opioid Receptor Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. Opioid receptors are distributed widely in the brain, and are found in the spinal cord and digestive tract. Opioid receptors are molecules, or sites, within the body that are activated by opioid substances. Opioid receptors inhibit the transmission of impulse in excitatory pathways within the human body system. These pathways include the serotonin, catecholamine, and substance P pathways, which are all implicated in pain perception and feelings of well-being. Opioid receptors are further subclassified into mu, delta, and kappa receptors. All the classes, while exhibiting differing modes of action, share some basic similarities. They all are driven by the potassium pump mechanism, which is found on the plasma membrane of the majority of cells. www.MedChemExpress.com 1 Opioid Receptor Agonists, Antagonists, Inhibitors, Activators & Modulators 6'-GNTI dihydrochloride 6-Alpha Naloxol Cat. No.: HY-110302 (Alpha-Naloxol) Cat. No.: HY-12799 6'-GNTI dihydrochloride, a κ-opioid receptor (KOR) 6-Alpha Naloxol(Alpha-Naloxol) is an opioid agonist, displays bias toward the activation of G antagonist closely related to naloxone; a human protein-mediated signaling over β-arrestin2 metabolite of naloxone. recruitment. 6'-GNTI 6'-GNTI dihydrochloride only activates the Akt pathway in striatal neurons. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg 6-beta-Naloxol D5 hydrochloride Ac-RYYRIK-NH2 (6β-Naloxol D5 hydrochloride) Cat. No.: HY-12780S Cat.
    [Show full text]
  • Analytical Reference Standards
    Analytical Reference Standards High Quality Noramco-qualified Standards Highly characterized, highly purified standards The United States Food and Drug Administration requires reference-standard materials to be of the highest quality, and thoroughly characterized, to assure identity, strength, and quality. Noramco offers well-characterized, highly purified analytical reference standards for routine analysis, method validation and development, commercial investigations, stability studies and other product development activities. Noramco’s reference standards program is focused on the synthesis of compounds of complex chemistry. Review our catalog of more than 175 reference standards. All reference materials may be ordered in a variety of quantities to meet your project requirements. Reference standard qualifications Noramco utilizes various sophisticated spectroscopic techniques to characterize each reference standard. Overall purity, or “Purity Factor,” is typically derived from 100% less the summation of inorganic, organic and solvent impurities. Table 1. Typical Certificate of Analysis includes: All analytical reference standards include a signed certificate of analysis (CoA) and 1.0 Appearance safety data sheet. The data within the CoA is 2.0 Identification based on information we believe to be highly accurate and reliable. Reference standards 3.0 Inorganic impurities supplied by Noramco is intended only for 4.0 Organic impurities analytical and research purposes and may not be used for human consumption. 5.0 Solvent impurities For
    [Show full text]