DOCSLIB.ORG

Long-Acting Testosterone Undecanoate for Parenteral Testosterone Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Long-Acting Testosterone Undecanoate for Parenteral Testosterone Therapy DRUG PROFILE Long-acting testosterone undecanoate for parenteral testosterone therapy Aksam A Yassin†, Testosterone as a compound for the treatment of testosterone deficiency has been Doris Huebler & available for almost 70 years; however, the pharmaceutical formulations have been less Farid Saad than ideal. Injectable testosterone esters have been used traditionally for treatment, but †Author for correspondence Clinic of Urology/Andrology, they generate supranormal testosterone levels shortly after the 2–3-weekly injections, Segeberger Kliniken, when testosterone levels then decline very rapidly becoming subnormal in the days Department of Urology, before the next injection. Testosterone undecanoate is a new injectable testosterone Rathausallee 94 a, 22846 Norderstedt-Hamburg, preparation with a considerably better pharmacokinetic profile. After two initial Germany; and Gulf Medical injections with a 6-week interval, the following intervals between two injections are College School of Medicine, almost always 12 weeks. Plasma testosterone levels with this preparation are almost Ajman, United Arab Emirates always in the normal range. Side effects experienced with conventional testosterone Tel.: +49 405 262 157 Fax: +49 405 262 820 esters are almost nil with this preparation. [email protected] Soon after its chemical identification more than Most forms of oral testosterone are alkylated 70 years ago, the male hormone testosterone at the 17α-carbon position, greatly reducing became pharmaceutically available. However, it their hepatic metabolism and improving their has taken a considerable time for convenient oral bioavailability. Unfortunately, these com- and safe preparations to be developed. The low pounds, such as 17α-methyl testosterone, are bioavailability, after both oral and parenteral associated with an unacceptably high rate of administration due to the short circulating half- hepatotoxic effects, including cholestatic jaun- life of testosterone, hampered its therapeutic use dice, peliosis hepatis and even liver tumors in a [1,2]. Among ways to circumvent these limita- third to half of long-term users [9–11]. As a result, tions, chemical modifications of the testoster- such 17α-alkylated forms of testosterone are not one molecule were developed allowing oral use, considered safe for long-term use by most although part some these turned out to be hepa- experts in the field [12]. totoxic. Subsequently, various parenteral testo- The only oral administration of testosterone sterone preparations were developed. Among that is currently safe is testosterone undecanoate the earliest were intramuscular injectable for- (TU), which is commercially available in many mulations of testosterone esterified with fatty countries. When administered orally, a portion of acids dissolved in a vegetable oil vehicle [3]. TU is absorbed via lymphatics and thereby These preparations remain the most cost-effec- bypasses hepatic first-pass metabolism [13–15]. TU tive and widely used worldwide. However, is lymphatically absorbed due to its long lipophilic injections of conventional testosterone fatty side chain. However, the absolute bioavailability acid esters (enanthate, cypionate, decanoate and of testosterone after oral TU administration is propionate) have an effective duration of action only approximately 6% [15], implying that most of of 1–2 weeks [4], as wider or narrower spacing an oral TU dose is absorbed via the portal circula- between injections leads to progressively more tion and metabolized by the liver. TU must be extreme excursions in serum testosterone con- administered orally in doses of 120–240 mg/day Keywords: injection interval, centrations with substantial supra- and sub- (divided in two-to-three administrations per day). pharmacokinetic profile, physiological serum concentrations, less well- The transdermal route for testosterone admin- testosterone esters, [5] testosterone treatment, sustained gonadotropin suppression and istration generates excellent pharmacokinetic testosterone undecanoate greater subjective symptoms of these wide fluc- profiles; however, patches can cause moderate to tuations [2]. Subdermal testosterone pellet severe skin reaction due to the vehicles (enhanc- implants or biodegradable microspheres allow ers) that facilitate testosterone absorption across longer application intervals, although handling the skin [16]. The newly available testosterone Future Drugs Ltd of these preparations is relatively difficult [6–8]. gels are safe and effective, but must be applied to 10.1586/14750708.3.6.709 © 2006 Future Drugs Ltd ISSN 1475-0708 Therapy (2006) 3(6), 709–721 709 DRUG PROFILE – Yassin, Huebler & Saad a fairly large area of skin and care must be taken able to develop a suitable intramuscular testo- to avoid inadvertent exposure to women and sterone preparation with a volume of 4 ml con- children [17–21]. taining 1000 mg of TU. At present, the Sustained- and controlled-release testoster- stability in climate zone II (25oC) lasts one buccal systems, including mucoadhesive 60 months [37]. Intramuscular TU is currently excipients, are now available in some countries not approved for use in the USA, but is pre- but require twice-daily administration. Venous scribed in Europe, Latin America and Asia drainage from the oral cavity flows directly to under the trade name Nebido®, and in Aus- the superior vena cava and, thus, hepatic first- tralia under the trade name Reandron 1000® pass metabolism is circumvented with these for the treatment of male hypogonadism. preparations [22–25]. In summary, each of these modes of testoster- Toxicology & pharmacology one delivery has drawbacks. The recent discov- The active pharmacological principle of LA-TU ery of steroidal and nonsteroidal selective is testosterone itself. After entering the periph- androgen receptor modulators (SARMs) could eral circulation, TU (molecular weight provide a promising alternative for testosterone 456.7 Da) is hydrolyzed to testosterone, which therapy, including hormonal male contracep- exerts its androgenic activity [14,38]. Therefore, tion. The identification of an orally bioavailable the toxicology of TU is the same as for other SARM with the ability to mimic the desired cleavable testosterone fatty acid esters, such as central and peripheral androgenic and anabolic testosterone propionate (three carbon atoms), effects of testosterone in a tissue-specific manner testosterone enanthate (TE; seven carbon atoms) and simultaneously avoid the undesirable or testosterone cypionate (eight carbon atoms). androgen effects (e.g., on prostate and skin) In contrast to these fatty acid esters, the kinetics would represent an important step in androgen for side-chain cleavage of the saturated aliphatic therapy [26–30]. However, most of these com- fatty acid undecanoic acid with 11 carbon atoms pounds are in very early phases of pharmaceuti- turned out to be considerably longer, permitting cal development and the availability on the much longer injection intervals and at the same market is expected in the more or less distant time preventing supra- or subphysiological future. That also applies to microencapsulation serum testosterone levels. of Leydig cells [31] and some possibilities of stem Nahrendorf and colleagues evaluated the influ- cell technology. ence of LA-TU treatment on left ventricular In a search for medium-term solutions to key remodeling following experimental myocardial problems of testosterone therapy, TU, for intra- infarction in male rats, as assessed by magnetic res- muscular administration was developed by onance imaging and in vivo hemodynamics [39]. Jenapharm GmbH & Co. KG, a subsidiary of The authors found no evidence for cardiac toxic- Schering AG in Berlin, Germany. The develop- ity of testosterone administration, despite a ten- ment of this long-acting TU (LA-TU) will now fold increase in testosterone serum levels, after be presented and discussed. TU administration compared with placebo administration. Neither infarct size nor proce- Development of LA-TU dure-related mortality was influenced by TU. For the development of an intramuscular long- On the contrary, there was a tendency to an acting testosterone preparation for male contra- improved hemodynamic outcome: left ventricu- ception, the WHO Special Programme of lar end diastolic pressure was reduced signifi- Research, Development and Research Training cantly in TU-treated animals together with wall in Human Reproduction initiated search activi- stress without differences in diastolic filling rates ties for identifying suitable fatty acid side chains following myocardial infarction. for esterification of testosterone [32]. It appeared Despite the fact that, after oral administra- that testosterone esterified with undecanoic acid tion, TU is well tolerated, the bioavailability shows ideal long-term kinetics [4,33–34]. The first leaves much to be desired. Täuber and colleagues TU preparation was developed in China [35–36]. reported that the mean absolute bioavailability Unfortunately, the injection volume of 8 ml for of testosterone after oral administration of TU to TU 1000 mg caused some problems at the local women was 6.83 ± 3.32%, whereas the mean injection site. Therefore, by use of a special absolute bioavailability of orally administered galenic formulation based on benzyl benzoate free testosterone was 3.64 ± 2.45% [15]. The and refined castor oil, Jenapharm/Schering were absorption of TU by the gut is erratic, resulting 710 Therapy (2006) 3(6) Testosterone
Load more

Recommended publications
  • Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals
    Journal of Clinical Medicine Review Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals Carlotta Cocchetti 1, Jiska Ristori 1, Alessia Romani 1, Mario Maggi 2 and Alessandra Daphne Fisher 1,* 1 Andrology, Women’s Endocrinology and Gender Incongruence Unit, Florence University Hospital, 50139 Florence, Italy; [email protected] (C.C); jiska.ristori@unifi.it (J.R.); [email protected] (A.R.) 2 Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, 50139 Florence, Italy; [email protected]fi.it * Correspondence: fi[email protected] Received: 16 April 2020; Accepted: 18 May 2020; Published: 26 May 2020 Abstract: Introduction: To date no standardized hormonal treatment protocols for non-binary transgender individuals have been described in the literature and there is a lack of data regarding their efficacy and safety. Objectives: To suggest possible treatment strategies for non-binary transgender individuals with non-standardized requests and to emphasize the importance of a personalized clinical approach. Methods: A narrative review of pertinent literature on gender-affirming hormonal treatment in transgender persons was performed using PubMed. Results: New hormonal treatment regimens outside those reported in current guidelines should be considered for non-binary transgender individuals, in order to improve psychological well-being and quality of life. In the present review we suggested the use of hormonal and non-hormonal compounds, which—based on their mechanism of action—could be used in these cases depending on clients’ requests. Conclusion: Requests for an individualized hormonal treatment in non-binary transgender individuals represent a future challenge for professionals managing transgender health care. For each case, clinicians should balance the benefits and risks of a personalized non-standardized treatment, actively involving the person in decisions regarding hormonal treatment.
    [Show full text]
  • Gender-Affirming Hormone Therapy
    GENDER-AFFIRMING HORMONE THERAPY Julie Thompson, PA-C Medical Director of Trans Health, Fenway Health March 2020 fenwayhealth.org GOALS AND OBJECTIVES 1. Review process of initiating hormone therapy through the informed consent model 2. Provide an overview of masculinizing and feminizing hormone therapy 3. Review realistic expectations and benefits of hormone therapy vs their associated risks 4. Discuss recommendations for monitoring fenwayhealth.org PROTOCOLS AND STANDARDS OF CARE fenwayhealth.org WPATH STANDARDS OF CARE, 2011 The criteria for hormone therapy are as follows: 1. Well-documented, persistent (at least 6mo) gender dysphoria 2. Capacity to make a fully informed decision and to consent for treatment 3. Age of majority in a given country 4. If significant medical or mental health concerns are present, they must be reasonably well controlled fenwayhealth.org INFORMED CONSENT MODEL ▪ Requires healthcare provider to ▪ Effectively communicate benefits, risks and alternatives of treatment to patient ▪ Assess that the patient is able to understand and consent to the treatment ▪ Informed consent model does not preclude mental health care! ▪ Recognizes that prescribing decision ultimately rests with clinical judgment of provider working together with the patient ▪ Recognizes patient autonomy and empowers self-agency ▪ Decreases barriers to medically necessary care fenwayhealth.org INITIAL VISITS ▪ Review history of gender experience and patient’s goals ▪ Document prior hormone use ▪ Assess appropriateness for gender affirming medical
    [Show full text]
  • Gender-Affirming Hormone Therapy
    GENDER-AFFIRMING HORMONE THERAPY Julie Thompson, PA-C Medical Director of Trans Health Fenway Health November 2019 fenwayhealth.org GOALS AND OBJECTIVES 1.Review process of initiating hormone therapy through the informed consent model 2.Provide an overview of masculinizing and feminizing hormone therapy 3.Review realistic expectations and benefits of hormone therapy vs their associated risks 4.Discuss recommendations for monitoring fenwayhealth.org PROTOCOLS AND STANDARDS OF CARE fenwayhealth.org WPATH STANDARDS OF CARE, 2011 The criteria for hormone therapy are as follows: 1. Well-documented, persistent (at least 6mo) gender dysphoria 2. Capacity to make a fully informed decision and to consent for treatment 3. Age of majority in a given country 4. If significant medical or mental health concerns are present, they must be reasonably well controlled fenwayhealth.org INFORMED CONSENT MODEL ▪ Requires healthcare provider to ▪ Effectively communicate benefits, risks and alternatives of treatment to patient ▪ Assess that the patient is able to understand and consent to the treatment ▪ Informed consent model does not preclude mental health care! ▪ Recognizes that prescribing decision ultimately rests with clinical judgment of provider working together with the patient ▪ Recognizes patient autonomy and empowers self-agency ▪ Decreases barriers to medically necessary care fenwayhealth.org INITIAL VISITS ▪ Review history of gender experience ▪ Document prior hormone use ▪ Review patient goals ▪ Assess appropriateness for gender affirming medical
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0296.191 A1 PATEL Et Al
    US 20140296.191A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0296.191 A1 PATEL et al. (43) Pub. Date: Oct. 2, 2014 (54) COMPOSITIONS OF PHARMACEUTICAL (52) U.S. Cl. ACTIVES CONTAINING DETHYLENE CPC ............... A61K 47/10 (2013.01); A61 K9/0019 GLYCOL MONOETHYLETHER OR OTHER (2013.01); A61 K9/0048 (2013.01); A61 K ALKYL DERVATIVES 45/06 (2013.01) USPC ........... 514/167: 514/177; 514/178: 514/450; (71) Applicant: THEMIS MEDICARE LIMITED, 514/334: 514/226.5: 514/449; 514/338; Mumbai (IN) 514/256; 514/570; 514/179; 514/174: 514/533; (72) Inventors: Dinesh Shantilal PATEL, Mumbai (IN); 514/629; 514/619 Sachin Dinesh PATEL, Mumbai (IN); Shashikant Prabhudas KURANI, Mumbai (IN); Madhavlal Govindlal (57) ABSTRACT PATEL, Mumbai (IN) (73) Assignee: THEMIS MEDICARE LIMITED, The present invention relates to pharmaceutical compositions Mumbai (IN) of various pharmaceutical actives, especially lyophilic and hydrophilic actives containing Diethylene glycol monoethyl (21) Appl. No.: 14/242,973 ether or other alkyl derivatives thereofas a primary vehicle and/or to pharmaceutical compositions utilizing Diethylene (22) Filed: Apr. 2, 2014 glycol monoethyl ether or other alkyl derivatives thereofas a primary vehicle or as a solvent system in preparation of Such (30) Foreign Application Priority Data pharmaceutical compositions. The pharmaceutical composi Apr. 2, 2013 (IN) ......................... 1287/MUMA2013 tions of the present invention are safe, non-toxic, exhibits enhanced physical stability compared to conventional formu Publication Classification lations containing such pharmaceutical actives and are Suit able for use as injectables for intravenous and intramuscular (51) Int. Cl. administration, as well as for use as a preformed solution/ A647/ (2006.01) liquid for filling in and preparation of capsules, tablets, nasal A6 IK 45/06 (2006.01) sprays, gargles, dermal applications, gels, topicals, liquid oral A6 IK9/00 (2006.01) dosage forms and other dosage forms.
    [Show full text]
  • Steroid Abuse by School Age Children
    epartment .D of .S Ju U s t ic U.S. Department of Justice e . n o i Drug Enforcement Administration t a r t is D in Office of Diversion Control r m ug d E t A nforcemen www.dea.gov www.DEAdiversion.usdoj.gov epartment .D of .S Ju U s t ic e . n o i t a r t is D in r m ug d E t A nforcemen Office of Diversion Control www.dea.gov STEROID ABUSE BY SCHOOL AGE CHILDREN nce viewed as a problem strictly associated with body builders, Ofitness “buffs,” and professional athletes, abuse of anabolic steroids by school age children has significantly increased over the past decade. The National Institute on Drug Abuse (NIDA) estimates that more than a half million 8th and 10th grade students are now using these dangerous drugs, and increasing numbers of high school seniors do not believe steroids are risky. Students are acquiring and taking anabolic steroids without any knowledge of the dangers associated with steroid abuse. The short- term adverse physical effects of anabolic steroid abuse are fairly well known. However, the long-term adverse physical effects of anabolic steroid abuse have not been studied, and as such, are not known. In addition, this type of abuse may result in harmful side-effects as well as serious injury and death. The abuser in most cases is unaware of these hidden dangers. Presented as a public service by: This guide will help you understand why steroids are being misused, Drug Enforcement Administration and how you can provide counseling and implement procedures to Office of Diversion Control educate our youth about the dangers of these drugs.
    [Show full text]
  • FDA Briefing Document NDA 206089 Testosterone Undecanoate
    FDA Briefing Document NDA 206089 Testosterone Undecanoate (proposed trade name Jatenzo) For replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) Meeting January 9, 2018 Division of Bone, Reproductive, and Urologic Products Office of New Drugs Division of Clinical Pharmacology 3 Office of Clinical Pharmacology Center for Drug Evaluation and Research 1 DISCLAIMER STATEMENT The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We have brought a new drug application (NDA 206089) for testosterone undecanoate oral capsules (proposed trade name, JATENZO), intended for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone sponsored by Clarus Therapeutics, Inc, to this Advisory Committee in order to gain the Committee’s insights and opinions. The background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting.
    [Show full text]
  • PUBLIC ASSESSMENT REPORT Decentralised Procedure Dienogest
    PUBLIC ASSESSMENT REPORT Decentralised Procedure Dienogest Aristo 2 mg Tabletten Procedure Number: DE/H/5431/001/DC Active Substance: Dienogest Dosage Form: Tablet Marketing Authorisation Holder in the RMS, Germany: Aristo Pharma GmbH Publication: 18.12.2019 This module reflects the scientific discussion for the approval of Dienogest Aristo 2 mg Tabletten. The procedure was finalised on 10.10.2019. TABLE OF CONTENTS I INTRODUCTION ......................................................................................................................... 4 II EXECUTIVE SUMMARY .......................................................................................................... 4 II.1 PROBLEM STATEMENT............................................................................................................... 4 II.2 ABOUT THE PRODUCT ................................................................................................................ 4 II.3 GENERAL COMMENTS ON THE SUBMITTED DOSSIER ............................................................... 5 II.4 GENERAL COMMENTS ON COMPLIANCE WITH GMP, GLP, GCP AND AGREED ETHICAL PRINCIPLES ........................................................................................................................................... 5 III SCIENTIFIC OVERVIEW AND DISCUSSION .................................................................... 6 III.1 QUALITY ASPECTS .................................................................................................................... 6 III.2
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,284,263 B1 Place (45) Date of Patent: Sep
    USOO6284263B1 (12) United States Patent (10) Patent No.: US 6,284,263 B1 Place (45) Date of Patent: Sep. 4, 2001 (54) BUCCAL DRUG ADMINISTRATION IN THE 4,755,386 7/1988 Hsiao et al. TREATMENT OF FEMALE SEXUAL 4,764,378 8/1988 Keith et al.. DYSFUNCTION 4,877,774 10/1989 Pitha et al.. 5,135,752 8/1992 Snipes. 5,190,967 3/1993 Riley. (76) Inventor: Virgil A. Place, P.O. Box 44555-10 5,346,701 9/1994 Heiber et al. Ala Kahua, Kawaihae, HI (US) 96743 5,516,523 5/1996 Heiber et al. 5,543,154 8/1996 Rork et al. ........................ 424/133.1 (*) Notice: Subject to any disclaimer, the term of this 5,639,743 6/1997 Kaswan et al. patent is extended or adjusted under 35 6,180,682 1/2001 Place. U.S.C. 154(b) by 0 days. * cited by examiner (21) Appl. No.: 09/626,772 Primary Examiner Thurman K. Page ASSistant Examiner-Rachel M. Bennett (22) Filed: Jul. 27, 2000 (74) Attorney, Agent, or Firm-Dianne E. Reed; Reed & Related U.S. Application Data ASSciates (62) Division of application No. 09/237,713, filed on Jan. 26, (57) ABSTRACT 1999, now Pat. No. 6,117,446. A buccal dosage unit is provided for administering a com (51) Int. Cl. ............................. A61F 13/02; A61 K9/20; bination of Steroidal active agents to a female individual. A61K 47/30 The novel buccal drug delivery Systems may be used in (52) U.S. Cl. .......................... 424/435; 424/434; 424/464; female hormone replacement therapy, in female 514/772.3 contraception, to treat female Sexual dysfunction, and to treat or prevent a variety of conditions and disorders which (58) Field of Search ....................................
    [Show full text]
  • Steroids and Other Appearance and Performance Enhancing Drugs (Apeds) Research Report
    Research Report Revised Febrero 2018 Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Table of Contents Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Introduction What are the different types of APEDs? What is the history of anabolic steroid use? Who uses anabolic steroids? Why are anabolic steroids misused? How are anabolic steroids used? What are the side effects of anabolic steroid misuse? How does anabolic steroid misuse affect behavior? What are the risks of anabolic steroid use in teens? How do anabolic steroids work in the brain? Are anabolic steroids addictive? How are anabolic steroids tested in athletes? What can be done to prevent steroid misuse? What treatments are effective for anabolic steroid misuse? Where can I get further information about steroids? References Page 1 Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Esta publicación está disponible para su uso y puede ser reproducida, en su totalidad, sin pedir autorización al NIDA. Se agradece la citación de la fuente, de la siguiente manera: Fuente: Instituto Nacional sobre el Abuso de Drogas; Institutos Nacionales de la Salud; Departamento de Salud y Servicios Humanos de los Estados Unidos. Introduction Appearance and performance enhancing drugs (APEDs) are most often used by males to improve appearance by building muscle mass or to enhance athletic performance. Although they may directly and indirectly have effects on a user’s mood, they do not produce a euphoric high, which makes APEDs distinct from other drugs such as cocaine, heroin, and marijuana. However, users may develop a substance use disorder, defined as continued use despite adverse consequences.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • The Combined Cardiac Effect of the Anabolic Steroid, Nandrolone And
    ù1. v -¿. rlc) 77.- *n*hi.rnool oowol,ù*o ffi"/fu -lo *rn*(o fii'o fio¿o¿¿, /v&"ùún lonno **al cooaiæe';¿vfl"- oã. Benjamin D. Phillis, B.Sc. (Hons) Phatmacology Depattment of Clinical & Experimental Pharmacology Ftome Rd. , Medical School Noth Adelaide Univetsity ADEIAIDE SA 5OOO û.)r.'-*hr/7enveltîù Foremost, I would like to thank my two supervisors for the direction that they have given this ptojecr. To Rod, for his unfailing troubleshooting abiJity and to Jenny fot her advice and ability to add scientific rigour' Many thanks to Michael Adams for his technical assistance and especially fot performing the surgery for the ischaemia-reperfusion projects and for his willingness to work late nights and public holidays. Lastly I would like to thank my v¡ife for her extreme patience during the tumult of the last 5 years. Her love, suppoït, patience and undetstanding have been invaluable in this endeavout. Beniamin D. Phillis Octobet,2005 ADE,I-AIDE ii T*(¿t of Ao,t",tù DECI.ARATION I ACKNOWLEDGEMENTS il TABLE OF CONTENTS UI ABBREVIATIONS x ABSTRACT )ilr CÉIAPTER t-l Inttoduction 1-1 1.1 Background 1,-1, 1.2What ate anabolic stetoids? 7-1 1,3 General pharmacology of Anabolic steroids t-2 '1,-2 1.3.1 Genomic effects of anabolic steroids 1.3.2 Non-genomic effects of anabolic steroids 1-3 1.4 Clinical use of AS 1.-4 1.5 Patterns of AS abuse 1.-4 1.5.1 Steroid abuse by athletes 1.-+ 1.5.2 Stetoid abuse by sedentary teenagers r-6 1.5.3 Prevalence of abuse 1-6 1.5.4 Abuse ptevalence in Australia 1.-9 1.6 Cardiotoxicity of anabolic steroids r-9 1.6.1 Reduced cotonary flow 1.-1.1, 1,.6.2 Dtect myocatdial eff ects 1-1 5 1.6.3 Hypertension 1-21 1.7 Difficulties associated with anabolic steroid research 1.-24 1-25 1.8 The polydrug abuse Phenomenon 1.9 The pharmacology of cocaine 1-26 1.10 Pteparations 1-28 1-29 1.11 Metabolism lll 1-30 1.
    [Show full text]
  • MEDICATION GUIDE JATENZO® (Juh-TEN-Zoh) (Testosterone
    MEDICATION GUIDE JATENZO® (juh-TEN-zoh) (testosterone undecanoate) capsules, for oral use CIII What is the most important information I should know about JATENZO? JATENZO can cause serious side effects, including: JATENZO can increase your blood pressure, which can increase your risk of having a heart attack or stroke and can increase your risk of death due to a heart attack or stroke. Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke. If your blood pressure increases while on JATENZO, blood pressure medicines may need to be started. If you are taking blood pressure medicines, new blood pressure medicines may need to be added or your current blood pressure medicines may need to be changed to control your blood pressure. If your blood pressure cannot be controlled, JATENZO may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with JATENZO. What is JATENZO? JATENZO is a prescription medicine that contains testosterone. JATENZO is used to treat adult men who have low or no testosterone due to certain medical conditions. It is not known if JATENZO is safe or effective in children younger than 18 years old. Improper use of JATENZO may affect bone growth in children. JATENZO is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your JATENZO in a safe place to protect it. Never give your JATENZO to anyone else, even if they have the same symptoms you have.
    [Show full text]