Advanced Control Specialty Formulary® Is a Guide Within Select Therapeutic Categories for Clients, Plan Members and Health Care Providers
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Endothelin System and Therapeutic Application of Endothelin Receptor
xperim ACCESS Freely available online & E en OPEN l ta a l ic P in h l a C r m f o a c l a o n l o r g u y o J Journal of ISSN: 2161-1459 Clinical & Experimental Pharmacology Research Article Endothelin System and Therapeutic Application of Endothelin Receptor Antagonists Abebe Basazn Mekuria, Zemene Demelash Kifle*, Mohammedbrhan Abdelwuhab Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia ABSTRACT Endothelin is a 21 amino acid molecule endogenous potent vasoconstrictor peptide. Endothelin is synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonic, and inflammatory cells. It acts through a seven transmembrane endothelin receptor A (ETA) and endothelin receptor B (ETB) receptors belongs to G protein-coupled rhodopsin-type receptor superfamily. This peptide involved in pathogenesis of cardiovascular disorder like (heart failure, arterial hypertension, myocardial infraction and atherosclerosis), renal failure, pulmonary arterial hypertension and it also involved in pathogenesis of cancer. Potentially endothelin receptor antagonist helps the treatment of the above disorder. Currently, there are a lot of trails both per-clinical and clinical on endothelin antagonist for various cardiovascular, pulmonary and cancer disorder. Some are approved by FAD for the treatment. These agents are including both selective and non-selective endothelin receptor antagonist (ETA/B). Currently, Bosentan, Ambrisentan, and Macitentan approved -
Sodium Phenylbutyrate (PB), Is a New Active Substance
SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of Ammonpas. This scientific discussion has been updated until 1 November 2001. For information on changes after this date please refer to module 8B. 1. Introduction Ammonaps, sodium phenylbutyrate (PB), is a new active substance. It is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase. It is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy. The dossier submitted in support of the application comprises data generated by the applicant: all chemical/pharmaceutical data, the two mutagenicity studies for Part III, and for Part IV, the bioequivalence study and a review of the US IND/NDA programme. Additional information was available from published literature. Urea cycle disorders (UCD) are inherited deficiencies of one of the enzymes involved in the urea cycle, by which ammonium is converted to urea. Ammonium is highly toxic to nerve cells and hyperammonaemia may result in metabolic derangement, leading to anorexia, lethargy, confusion, coma, brain damage, and death. The most severe forms of UCDs occur early in life (complete enzyme deficiencies). The classic neonatal presentation of all the UCD (with the exception of arginase deficiency) is quite uniform and includes, after a short symptom-free interval of one to five days, poor feeding, vomiting, lethargy, muscular hypotonia, hyperventilation, irritability and convulsions. -
Endothelin-Receptor Antagonists Are Proapoptotic and Antiproliferative in Human Colon Cancer Cells
British Journal of Cancer (2003) 88, 788 – 795 & 2003 Cancer Research UK All rights reserved 0007 – 0920/03 $25.00 www.bjcancer.com Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells 1 1 ,1 L Peduto Eberl , R Bovey and L Juillerat-Jeanneret* 1 University Institute of Pathology, CHUV, University of Lausanne, Bugnon 25, CH1011 Lausanne, Switzerland Endothelin (ET)-1 can act as an autocrine/paracrine growth factor or an antiapoptotic factor in human cancers. To study the role of ET-1 in human colon cancer, proliferation and apoptosis of colon carcinoma cells was investigated using human HT-29 and SW480 colon carcinoma cells. ET-1 was secreted by these cells. Treatment of cells with bosentan, a dual ETA/B-receptor antagonist, decreased cell number. Inhibition of DNA synthesis by bosentan was observed only in the presence of serum. Exogenously added ET-1 did not increase DNA synthesis in serum-deprived cells. SW480 cells were sensitive and HT-29 cells were resistant to FasL- induced apoptosis. Bosentan sensitised resistant HT-29 cells to FasL-induced, caspase-mediated apoptosis, but not to TNF-a-induced apoptosis. Bosentan and/or FasLigand (FasL) did not modulate the expression of caspase-8 or FLIP. Bosentan sensitisation to À13 À10 À9 À7 apoptosis was reversed by low concentrations (10 –10 M), but not by high concentrations (10 –10 M) of ET-1. These results suggest that the binding of ET-1 to high-affinity sites inhibits FasL-induced apoptosis, while the binding of either ET-1 or receptor antagonists to low-affinity sites promotes FasL-induced apoptosis. -
Human Chorionic Gonadotropin (HCG), a Polypeptide Hormone Produced by the Human
45792G/Revised: April 2011 CHORIONIC GONADOTROPIN FOR INJECTION, USP DESCRIPTION: Human chorionic gonadotropin (HCG), a polypeptide hormone produced by the human placenta, is composed of an alpha and a beta sub-unit. The alpha sub-unit is essentially identical to the alpha sub-units of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to the alpha sub-unit of human thyroid-stimulating hormone (TSH). The beta sub-units of these hormones differ in amino acid sequence. Chorionic gonadotropin is obtained from the human pregnancy urine. It is standardized by a biological assay procedure. Chorionic Gonadotropin for Injection, USP is available in multiple dose vials containing 10,000 USP Units with accompanying Bacteriostatic Water for Injection for reconstitution. When reconstituted with 10 mL of the accompanying diluent each vial contains: Chorionic gonadotropin 10,000 Units Mannitol 100 mg Benzyl alcohol 0.9% Water for Injection q.s. Buffered with dibasic sodium phosphate and monobasic sodium phosphate. Hydrochloric acid and/or sodium hydroxide may have been used for pH adjustment (6.0 Reference ID: 2933198 8.0). Nitrogen gas is used in the freeze drying process. CLINICAL PHARMACOLOGY: The action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well. It stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone. Androgen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present. -
Gonadotropin and Testosterone Measurements After
Pediat. Res. 10: 46-51 (1976) Estradiol puberty estrogen sexual differentiation gonadotropins testosterone maturation Gonadotropin and Testosterone Measurements after Estrogen Administration to Adult Men, Prepubertal and Pubertal Boys, and Men with Hypogonadotropism: Evidence for Maturation of Positive Feedback in the Male HOWARD E. KULIN"" AND EDWARD 0. REITER Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Extract MATERIALS AND METHODS Nineteen male subjects were given five daily injections of SUBJECTS 17~-estradiol and circulating levels of estradiol (E 2 ), testosterone (T), and gonadotropins were determined by radioimmunoassay Seven normal, adult men (ages 20-22) and one male (age 21) before, during, and after the steroid course. Peak levels of E 2 with the syndrome of vanishing testes (I) were hospitalized for attained during the 5 days of treatment ranged from 173-577 pg/ml. study at the Clinical Center of the National Institutes of Health. Four of seven normal adult men and one castrate man demonstrated Each patient was given five daily intramuscular injections of IO or suppression of follicle-stimulating hormone ( FSH) and luteinizing 15 ,ug/kg body weight of 17~-estradiol (E2 ) (20) and blood samples hormone ( LH) with a subsequent rise in LH ( positive feedback) were obtained every 12-24 hr before, during, and after the estrogen while E 2 levels remained elevated. A rise in T was associated with course (see Table I). the LH increment in the four normal men. Nine pre-, early, or Nine endocrinologically normal boys between the ages of 7 and midpubertal boys and two men with hypogonadotropic hypogo 18 were studied in the course of evaluation for short stature, nadism displayed only gonadotropin suppression after E 2 adminis precocious puberty, or delayed adolescence. -
Chorionic Gonadotropin Human (C0684)
Chorionic gonadotropin human Product Number C 0684 Storage Temperature -0 °C Product Description When hCG was used in combination with recombinant CAS Number: 9002-61-3 interferon-γ, there was a significant cooperative pI = 2.951 induction of nitric oxide synthesis (iNOS) in a dose- Extinction Coefficient: E1% = 3.88 (278nm)2 dependent manner in mouse peritoneal macrophages Synonym: Choriogonin, hCG suggesting that hCG may provide a second signal for synergistic induction of NO synthesis.9 The molecular weight is approximately 37.9 kDa (with approximately 31% carbohydrate by weight). The Precautions and Disclaimer theoretical molecular weight is 37.9 kDa based on the For Laboratory Use Only. Not for drug, household or native form, which contains 2 subunits. The α subunit other uses. has a molecular weight of 14.9 kDa of which approximately 10.2 kDa is for the polypeptide and Preparation Instructions approximately 4.7 kDa for the carbohydrate. The hCG is soluble in water and aqueous buffers such β subunit has a molecular weight of 23 kDa of which phosphate buffer. hCG is also soluble in aqueous approximately 16.0 kDa is for the polypeptide and glycerol and glycols and is insoluble in ethanol.1 approximately 7.0 kDa is for the carbohydrate.3,4,5 Solutions should be sterile filtered and not autoclaved. Product Number C 0684 is sterile filtered and contains Storage/Stability approximately 1,000 I.U. per vial. Dilute aqueous solutions undergo rapid loss of activity when stored frozen, or heated, or if excess acid or hCG is a glycoprotein hormone produced by the base is added. -
Self-Nano-Emulsifying Drug-Delivery Systems: from the Development to the Current Applications and Challenges in Oral Drug Delivery
pharmaceutics Review Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery Aristote B. Buya 1,2 , Ana Beloqui 1, Patrick B. Memvanga 2 and Véronique Préat 1,* 1 Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium; [email protected] (A.B.B.); [email protected] (A.B.) 2 Pharmaceutics and Phytopharmaceutical Drug Development Research Group, Faculty of Pharmaceutical Sciences, University of Kinshasa, Kinshasa XI BP 212, Democratic Republic of the Congo; [email protected] * Correspondence: [email protected]; Tel.: +32-27647309 Received: 3 November 2020; Accepted: 5 December 2020; Published: 9 December 2020 Abstract: Approximately one third of newly discovered drug molecules show insufficient water solubility and therefore low oral bio-availability. Self-nano-emulsifying drug-delivery systems (SNEDDSs) are one of the emerging strategies developed to tackle the issues associated with their oral delivery. SNEDDSs are composed of an oil phase, surfactant, and cosurfactant or cosolvent. SNEDDSs characteristics, their ability to dissolve a drug, and in vivo considerations are determinant factors in the choice of SNEDDSs excipients. A SNEDDS formulation can be optimized through phase diagram approach or statistical design of experiments. The characterization of SNEDDSs includes multiple orthogonal methods required to fully control SNEDDS manufacture, stability, and biological fate. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The transformation of liquid SNEDDSs into solid dosage forms has been shown to increase the stability and patient compliance. -
Horizon Therapeutics Public Annual Report 2020
Horizon Therapeutics Public Annual Report 2020 Form 10-K (NASDAQ:HZNP) Published: February 26th, 2020 PDF generated by stocklight.com octb inte UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-35238 HORIZON THERAPEUTICS PUBLIC LIMITED COMPANY (Exact name of Registrant as specified in its charter) Ireland Not Applicable (State or other jurisdiction of (I.R.S. Employer incorporation or organization) Identification No.) Connaught House, 1st Floor 1 Burlington Road, Dublin 4, D04 C5Y6, Ireland Not Applicable (Address of principal executive offices) (Zip Code) 011 353 1 772 2100 (Registrant’s telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: Title of Each Class Trading Symbol Name of Each Exchange on Which Registered Ordinary shares, nominal value $0.0001 per share HZNP The Nasdaq Global Select Market Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☒ No ☐. Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒. Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. -
Advanced Prostate Cancer: Developing Gonadotropin- Releasing Hormone Analogues Guidance for Industry
Advanced Prostate Cancer: Developing Gonadotropin- Releasing Hormone Analogues Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to https://www.regulations.gov. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document, contact Elaine Chang at 240-402-2628. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) July 2019 Clinical/Medical Advanced Prostate Cancer: Developing Gonadotropin- Releasing Hormone Analogues Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: [email protected] https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation -
Comparison of Pharmacological Activity of Macitentan and Bosentan in Preclinical Models of Systemic and Pulmonary Hypertension
LFS-13929; No of Pages 7 Life Sciences xxx (2014) xxx–xxx Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmonary hypertension Marc Iglarz ⁎, Alexandre Bossu, Daniel Wanner, Céline Bortolamiol, Markus Rey, Patrick Hess, Martine Clozel Drug Discovery Department, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland article info abstract Article history: Aims: The endothelin (ET) system is a tissular system, as the production of ET isoforms is mostly autocrine or Received 29 October 2013 paracrine. Macitentan is a novel dual ETA/ETB receptor antagonist with enhanced tissue distribution and Accepted 12 February 2014 sustained receptor binding properties designed to achieve a more efficacious ET receptor blockade. To determine Available online xxxx if these features translate into improved efficacy in vivo, a study was designed in which rats with either systemic or pulmonary hypertension and equipped with telemetry were given macitentan on top of maximally effective Keywords: doses of another dual ET /ET receptor antagonist, bosentan, which does not display sustained receptor occupan- Endothelin A B Pharmacology cy and shows less tissue distribution. – Blood pressure Main methods: After establishing dose response curves of both compounds in conscious, hypertensive Dahl salt- Pulmonary hypertension sensitive and pulmonary hypertensive bleomycin-treated rats, macitentan was administered on top of the max- Rat imal effective dose of bosentan. Key findings: In hypertensive rats, macitentan 30 mg/kg further decreased mean arterial blood pressure (MAP) by 19 mm Hg when given on top of bosentan 100 mg/kg (n =9,p b 0.01 vs. -
WSAVA List of Essential Medicines for Cats and Dogs
The World Small Animal Veterinary Association (WSAVA) List of Essential Medicines for Cats and Dogs Version 1; January 20th, 2020 Members of the WSAVA Therapeutic Guidelines Group (TGG) Steagall PV, Pelligand L, Page SW, Bourgeois M, Weese S, Manigot G, Dublin D, Ferreira JP, Guardabassi L © 2020 WSAVA All Rights Reserved Contents Background ................................................................................................................................... 2 Definition ...................................................................................................................................... 2 Using the List of Essential Medicines ............................................................................................ 2 Criteria for selection of essential medicines ................................................................................. 3 Anaesthetic, analgesic, sedative and emergency drugs ............................................................... 4 Antimicrobial drugs ....................................................................................................................... 7 Antibacterial and antiprotozoal drugs ....................................................................................... 7 Systemic administration ........................................................................................................ 7 Topical administration ........................................................................................................... 9 Antifungal drugs ..................................................................................................................... -
The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men
ORIGINAL ARTICLE Endocrine Research The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men M. Y. Roth, S. T. Page, K. Lin, B. D. Anawalt, A. M. Matsumoto, B. Marck, W. J. Bremner, and J. K. Amory Downloaded from https://academic.oup.com/jcem/article/96/4/1175/2720870 by guest on 02 October 2021 Departments of Internal Medicine (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.) and Obstetrics and Gynecology (K.L.) and Center for Research in Reproduction and Contraception (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.), University of Washington, Seattle, Washington 91895; and Geriatric Research (B.M.), Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98105 Introduction: Concentrations of intratesticular (IT) testosterone (T) are known to be 100–200 times those of serum T; however, the IT concentrations of T’s precursors, their testicular to serum gra- dients, gonadotropin dependence, and response to stimulation with human chorionic gonado- tropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the adminis- tration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. Methods: We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d.