DOCSLIB.ORG

Assessment Report

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Assessment Report 25 January 2018 EMA/88321/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report EnCyzix International non-proprietary name: enclomifene Procedure No. EMEA/H/C/004198/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Administrative information Name of the medicinal product: EnCyzix Applicant: Renable Pharma Limited 20-22 Bedford Row WC1R 4JS UNITED KINGDOM Active substance: ENCLOMIFENE CITRATE International Non-proprietary Name/Common Enclomifene Name: Not assigned Pharmaco-therapeutic group (ATC Code): Treatment of hypogonadotropic hypogonadism (secondary hypogonadism) in Therapeutic indication(s): adult men aged ≤60 years with a body mass index (BMI) ≥25 kg/m2 which has been confirmed by clinical features and biochemical tests in patients which have not responded to diet and exercise Pharmaceutical form(s): Capsule, hard Strength(s): 8.5 mg and 17 mg Route(s) of administration: Oral use Packaging: bottle (HDPE) Package size(s): 30 capsules EMA/88321/2018 Page 2/111 Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ..................................................................................... 7 1.2. Steps taken for the assessment of the product ........................................................ 8 2. Scientific discussion ................................................................................ 9 2.1. Problem statement ............................................................................................... 9 2.1.1. Disease or condition .......................................................................................... 9 2.1.2. Epidemiology .................................................................................................... 9 2.1.3. Aetiology and pathogenesis ................................................................................ 9 2.1.4. Clinical presentation and diagnosis .................................................................... 10 2.1.5. Management ................................................................................................... 10 2.2. Quality aspects .................................................................................................. 11 2.2.1. Introduction.................................................................................................... 11 2.2.2. Active Substance ............................................................................................. 11 General information .................................................................................................. 11 Manufacture, characterisation and process controls ....................................................... 12 Specification ............................................................................................................ 13 Stability................................................................................................................... 13 2.2.3. Finished Medicinal Product ................................................................................ 14 Description of the product and Pharmaceutical development .......................................... 14 Manufacture of the product and process controls .......................................................... 15 Product specification ................................................................................................. 15 Stability of the product .............................................................................................. 15 Adventitious agents .................................................................................................. 16 2.2.4. Discussion on chemical, pharmaceutical and biological aspects.............................. 16 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 16 2.2.6. Recommendations for future quality development ............................................... 16 2.3. Non-clinical aspects ............................................................................................ 17 2.3.1. Introduction.................................................................................................... 17 2.3.2. Pharmacology ................................................................................................. 17 2.3.3. Pharmacokinetics ............................................................................................ 19 2.3.4. Toxicology ...................................................................................................... 22 2.3.5. Ecotoxicity/environmental risk assessment ......................................................... 29 2.3.6. Discussion on non-clinical aspects ..................................................................... 30 2.3.7. Conclusion on the non-clinical aspects ............................................................... 33 2.4. Clinical aspects .................................................................................................. 33 2.4.1. Introduction.................................................................................................... 33 2.4.2. Pharmacokinetics ............................................................................................ 36 2.4.3. Pharmacodynamics .......................................................................................... 44 2.4.4. Discussion on clinical pharmacology ................................................................... 48 EMA/88321/2018 Page 3/111 2.4.5. Conclusions on clinical pharmacology ................................................................. 50 2.5. Clinical efficacy .................................................................................................. 50 2.5.1. Dose response studies ..................................................................................... 50 2.5.2. Main studies ................................................................................................... 50 2.5.3. Discussion on clinical efficacy ............................................................................ 87 2.5.4. Conclusions on the clinical efficacy .................................................................... 90 2.6. Clinical safety .................................................................................................... 90 2.6.1. Discussion on clinical safety .............................................................................. 99 2.7. Risk Management Plan ...................................................................................... 101 2.8. Pharmacovigilance ........................................................................................... 101 2.9. New Active Substance ...................................................................................... 101 2.10. Product information ........................................................................................ 101 2.10.1. User consultation ......................................................................................... 101 3. Benefit-Risk Balance ........................................................................... 102 3.1. Therapeutic Context ......................................................................................... 102 3.1.1. Disease or condition ...................................................................................... 102 3.1.2. Available therapies and unmet medical need ..................................................... 102 3.1.3. Main clinical studies ....................................................................................... 102 3.2. Favourable effects ............................................................................................ 103 3.3. Uncertainties and limitations about favourable effects ........................................... 104 3.4. Unfavourable effects ......................................................................................... 105 3.5. Uncertainties and limitations about unfavourable effects ....................................... 105 3.6. Effects Table .................................................................................................... 105 3.7. Benefit-risk assessment and discussion ............................................................... 107 3.7.1. Importance of favourable and unfavourable effects ............................................ 107 3.7.2. Balance of benefits and risks .......................................................................... 107 3.8. Conclusions ..................................................................................................... 107 4. Recommendations ............................................................................... 107 Divergent position – Encyzix (EMEA/H/C/004198) ................................ 110 EMA/88321/2018 Page 4/111 List of abbreviations ACTH Adrenocorticotropic Hormone AE Adverse Event ALT Alanine Transaminase AST Aspartate Transaminase AUC Area Under the Curve BCS Biopharmaceutics Classification System b.i.d bis in die (twice a day) BMI Body Mass Index
Load more

Recommended publications
  • Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
    Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs.
    [Show full text]
  • Clomifene Citrate(BANM, Rinnm) ⊗
    2086 Sex Hormones and their Modulators Profasi; UK: Choragon; Ovitrelle; Pregnyl; USA: Chorex†; Choron; Gonic; who received the drug for a shorter period.6 No association be- 8. Werler MM, et al. Ovulation induction and risk of neural tube Novarel; Ovidrel; Pregnyl; Profasi; Venez.: Ovidrel; Pregnyl; Profasi†. tween gonadotrophin therapy and ovarian cancer was noted in defects. Lancet 1994; 344: 445–6. Multi-ingredient: Ger.: NeyNormin N (Revitorgan-Dilutionen N Nr this study. The conclusions of this study were only tentative, 9. Greenland S, Ackerman DL. Clomiphene citrate and neural tube 65)†; Mex.: Gonakor. defects: a pooled analysis of controlled epidemiologic studies since the numbers who developed ovarian cancer were small; it and recommendations for future studies. Fertil Steril 1995; 64: has been pointed out that a successfully achieved pregnancy may 936–41. reduce the risk of some other cancers, and that the risks and ben- 10. Whiteman D, et al. Reproductive factors, subfertility, and risk efits of the procedure are not easy to balance.7 A review8 of epi- of neural tube defects: a case-control study based on the Oxford Clomifene Citrate (BANM, rINNM) ⊗ Record Linkage Study Register. Am J Epidemiol 2000; 152: demiological and cohort studies concluded that clomifene was 823–8. Chloramiphene Citrate; Citrato de clomifeno; Clomifène, citrate not associated with any increase in the risk of ovarian cancer 11. Sørensen HT, et al. Use of clomifene during early pregnancy de; Clomifeni citras; Clomiphene Citrate (USAN); Klomifeenisi- when used for less than 12 cycles, but noted conflicting results, and risk of hypospadias: population based case-control study.
    [Show full text]
  • Clomid (Clomiphene Citrate USP)
    PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory Agent sanofi-aventis Canada Inc. Date of Revision: 2905 Place Louis-R.-Renaud August 9, 2013 Laval, Quebec H7V 0A3 Submission Control No.: 165671 s-a Version 5.0 dated August 9, 2013 Page 1 of 23 PRODUCT MONOGRAPH PrCLOMID® (clomiphene citrate USP) 50 mg Tablets Ovulatory agent. ACTION AND CLINICAL PHARMACOLOGY CLOMID (clomiphene citrate) is an orally-administered, non-steroidal agent which may induce ovulation in anovulatory women in appropriately selected cases.1-16 The ovulatory response to cyclic CLOMID therapy appears to be mediated through increased output of pituitary gonadotropins, which in turn stimulate the maturation and endocrine activity of the ovarian follicle and the subsequent development and function of the corpus luteum. The role of the pituitary is indicated by increased plasma levels of gonadotropins and by the response of the ovary, as manifested by increased plasma level of estradiol. Antagonism of competitive inhibition of endogenous estrogen may play a role in the action of CLOMID on the hypothalamus. CLOMID is a drug of considerable pharmacologic potency. Its administration should be preceded by careful evaluation and selection of the patient, and must be accompanied by close attention to the timing of the dose. With conservative selection and management of the patient, CLOMID has been demonstrated to be a useful therapy for the anovulatory patient. Based on studies with 14C-labeled clomiphene, the drug is readily absorbed orally in humans, and is excreted principally in the feces. Cumulative excretion of the 14C-label averaged 51% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 8% and mean fecal excretion of 42%; less than 1% per day was excreted in fecal and urine samples collected from 31 to 53 days after 14C-labelled clomiphene administration.
    [Show full text]
  • Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – an Evidence Based Approach
    1 Management of Women with Clomifene Citrate Resistant Polycystic Ovary Syndrome – An Evidence Based Approach Hatem Abu Hashim Department of Obstetrics & Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 1. Introduction World Health Organisation (WHO) type II anovulation is defined as normogonadotrophic normoestrogenic anovulation and occurs in approximately 85% of anovulatory patients. Polycystic ovary syndrome (PCOS) is the most common form of WHO type II anovulatory infertility and is associated with hyperandrogenemia (1,2). Moreover, PCOS is the most common endocrine abnormality in reproductive age women. The prevalence of PCOS is traditionally estimated at 4% to 8% from studies performed in Greece, Spain and the USA (3-6). The prevalence of PCOS has increased with the use of different diagnostic criteria and has recently been shown to be 11.9 ± 2.4% -17.8 ± 2.8 in the first community-based prevalence study based on the current Rotterdam diagnostic criteria compared with 10.2 ± 2.2% -12.0 ± 2.4% and 8.7 ± 2.0% using National Institutes of Health criteria and Androgen Excess Society recommendations respectively (7). Importantly, 70% of women in this recent study were undiagnosed (7). Clomiphene citrate (CC) is still holding its place as the first-line therapy for ovulation induction in these patients (2,8,9). CC contains an unequal mixture of two isomers as their citrate salts, enclomiphene and zuclomiphene. Zuclomiphene is much the more potent of the two for induction of ovulation, accounts for 38% of the total drug content of one tablet and has a much longer half-life than enclomiphene, being detectable in plasma 1 month following its administration (10).
    [Show full text]
  • Clomifene Or Letrozole Ovulation Induction Treatment
    What happens next? For most women (once the correct dose has been established) we would encourage you to continue for six months without having to be scanned. After this, if you are still not pregnant, please ring your Fertility Nurse for advice. If, during the time you are receiving treatment, your periods become irregular ie. longer than 33-34 days, or you lose over a stone in weight (gaining is not an option!), please contact your Fertility Nurse. Clomifene or Letrozole Good Luck (Please call if you are pregnant!) Ovulation Induction Cornwall Centre for Reproductive Medicine treatment Wheal Unity Clinic Administrator – 01872 253044 Fertility Nurses – 01872 252061 If you would like this leaflet in large print, braille, audio version or in another language, please contact the General Office on 01872 252690 RCHT 557 © RCHT Design & Publications 2002 Revised 12/2018 V3 Review due 12/2021 What is clomifene? There is also a theoretical, but not proven, concern that prolonged use may Clomifene citrate or Letrozole are the most commonly used drug in the make the development of ovarian cancer more likely. Therefore it is treatment of women who fail to ovulate (produce an egg) regularly. Clomifene recommended to be taken for a year only, taking it for any longer is unlikely to or Letrozole drugs have the effect of boosting the production of those give any significant benefit. hormones that stimulate eggs to grow. When and how is it taken? Does it work for everyone? Take clomifene/letrozole for four days starting the day after your period starts Over half of women will respond to clomifene/letrozole treatment (more so if (ie.
    [Show full text]
  • 6. Endocrine System 6.1 - Drugs Used in Diabetes Also See SIGN 116: Management of Diabetes, 2010
    1 6. Endocrine System 6.1 - Drugs used in Diabetes Also see SIGN 116: Management of Diabetes, 2010 http://www.sign.ac.uk/guidelines/fulltext/116 Insulin Prescribing Guidance in Type 2 Diabetes http://www.fifeadtc.scot.nhs.uk/media/6978/insulin-prescribing-in-type-2-diabetes.pdf 6.1.1 Insulins (Type 2 Diabetes) 6.1.1.1 Short Acting Insulins 1st Choice S – Insuman ® Rapid (Human Insulin) S – Humulin S ® S – Actrapid ® 2nd Choice S – Insulin Aspart (NovoRapid ®) (Insulin Analogues) S – Insulin Lispro (Humalog ®) 6.1.1.2 Intermediate and Long Acting Insulins 1st Choice S – Isophane Insulin (Insuman Basal ®) (Human Insulin) S – Isophane Insulin (Humulin I ®) S – Isophane Insulin (Insulatard ®) 2nd Choice S – Insulin Detemir (Levemir ®) (Insulin Analogues) S – Insulin Glargine (Lantus ®) Biphasic Insulins 1st Choice S – Biphasic Isophane (Human Insulin) (Insuman Comb ® ‘15’, ‘25’,’50’) S – Biphasic Isophane (Humulin M3 ®) 2nd Choice S – Biphasic Aspart (Novomix ® 30) (Insulin Analogues) S – Biphasic Lispro (Humalog ® Mix ‘25’ or ‘50’) Prescribing Points For patients with Type 1 diabetes, insulin will be initiated by a diabetes specialist with continuation of prescribing in primary care. Insulin analogues are the preferred insulins for use in Type 1 diabetes. Cartridge formulations of insulin are preferred to alternative formulations Type 2 patients who are newly prescribed insulin should usually be started on NPH isophane insulin, (e.g. Insuman Basal ®, Humulin I ®, Insulatard ®). Long-acting recombinant human insulin analogues (e.g. Levemir ®, Lantus ®) offer no significant clinical advantage for most type 2 patients and are much more expensive. In terms of human insulin. The Insuman ® range is currently the most cost-effective and preferred in new patients.
    [Show full text]
  • Index to the NLM Classification 2011
    National Library of Medicine Classification 2011 Index Disease see Tyrosinemias 1-8 5,12-diHETE see Leukotriene B4 1,2-Benzopyrones see Coumarins 5,12-HETE see Leukotriene B4 1,2-Dibromoethane see Ethylene Dibromide 5-HT see Serotonin 1,8-Dihydroxy-9-anthrone see Anthralin 5-HT Antagonists see Serotonin Antagonists 1-Oxacephalosporin see Moxalactam 5-Hydroxytryptamine see Serotonin 1-Propanol 5-Hydroxytryptamine Antagonists see Serotonin Organic chemistry QD 305.A4 Antagonists Pharmacology QV 82 6-Mercaptopurine QV 269 1-Sar-8-Ala Angiotensin II see Saralasin 7S RNA see RNA, Small Nuclear 1-Sarcosine-8-Alanine Angiotensin II see Saralasin 8-Hydroxyquinoline see Oxyquinoline 13-cis-Retinoic Acid see Isotretinoin 8-Methoxypsoralen see Methoxsalen 15th Century History see History, 15th Century 8-Quinolinol see Oxyquinoline 16th Century History see History, 16th Century 17 beta-Estradiol see Estradiol 17-Ketosteroids WK 755 A 17-Oxosteroids see 17-Ketosteroids A Fibers see Nerve Fibers, Myelinated 17th Century History see History, 17th Century Aardvarks see Xenarthra 18th Century History see History, 18th Century Abate see Temefos 19th Century History see History, 19th Century Abattoirs WA 707 2',3'-Cyclic-Nucleotide Phosphodiesterases QU 136 Abbreviations 2,4-D see 2,4-Dichlorophenoxyacetic Acid Chemistry QD 7 2,4-Dichlorophenoxyacetic Acid General P 365-365.5 Organic chemistry QD 341.A2 Library symbols (U.S.) Z 881 2',5'-Oligoadenylate Polymerase see Medical W 13 2',5'-Oligoadenylate Synthetase By specialties (Form number 13 in any NLM
    [Show full text]
  • QSAR Modeling
    Best practices for developing predictive QSAR models Alexander Tropsha Laboratory for Molecular Modeling and Carolina Center for Exploratory Cheminformatics Research School of Pharmacy UNC-Chapel Hill OUTLINE • Introduction: Brief outline of the QSAR approach • Why models fail (bad practices) • Good practices. – Predictive QSAR Modeling Workflow – Examples of the Workflow applications – Emerging applications of QSAR: chemocentric informatics • Conclusions: QSAR modeling is a decision support The rumors of QSAR demise have been greatly exaggerated 100,000 4500 90,000 4000 number of QSAR 80,000 Number of compounds papers in PubMed 3500 70,000 in CAS (in 1000s) 3000 60,000 2500 50,000 2000 40,000 Number of protein 1500 Structures in PDB 30,000 1000 20,000 500 10,000 0 0 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 Graphs are courtesy of Prof. A. Cherkasov Principles of QSAR modeling Introduction O N C 0.613 O O N 0.380 A -0.222 O D C M N O E 0.708 N S O Quantitative 1.146 T P N C O R 0.491 N Structure I O I 0.301 O P Activity N 0.141 V U O T Relationships N O 0.956 I N O R N 0.256 S D 0.799 T O 1.195 N Y S 1.005 Principles of QSAR/QSPR modeling Introduction O N C 0.613 O O N 0.380 P -0.222 O D R M N O E 0.708 N S O Quantitative 1.146 O P N C O R 0.491 N Structure P O I 0.301 O P Property N 0.141 E U O T Relationships N O 0.956 R N O R N 0.256 S D 0.799 T O 1.195 N Y S 1.005 The utility of QSAR models CHEMICAL
    [Show full text]
  • Electrochemical Behaviour and Quantitative Determination Of
    Int J Pharma Res Health Sci. 2017; 5 (6): 2014-18 DOI:10.21276/ijprhs.2017.06.22 Reddy et al CODEN (USA)-IJPRUR, e-ISSN: 2348-6465 International Journal of Pharma Research and Health Sciences Available online at www.pharmahealthsciences.net Original Article Electrochemical Behaviour and Quantitative Determination of Clomifene in Pharmaceutical Formulations C Nageswara Reddy1,*, P Sandhya 3, P R Prasad 2, N Y Sreedhar 2 1Department of Chemistry, Govt. Degree & P.G. College, Puttur-517 583, A.P., India. 2Electroanalytical Lab, Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, A.P, India. 3Department of Chemistry, Sri Padmavati Mahila Visvavidyalayam, Tirupati-517 502, A.P, India. ARTICLE INFO ABSTRACT Received: 11 Nov 2017 The electrochemical behaviour of clomifene was studied and determined in pharmaceutical Accepted: 18 Dec 2017 formulations. The drug of clomifene was electrochemically examined by cyclic and differential pulse voltammetry using a glassy carbon electrode (GCE). The obtained results showed that, the Britton Robinson buffer with pH 4.0 was the best medium for reduction of clomifene on the glassy carbon electrode at the peak potential -1.01 V. The range of linearity was found to be from 0.20 μg mL-1 to 60.0 μg mL-1 (R2 = 0.994) with limit of detection (LOD) 0.168 μg mL-1 and limit of quantification (LOQ) was 0.511 μg mL-1. Differential pulse voltammetric method was successfully applied for the electrochemical determination of clomifene in pharmaceutical formulations ______ Keywords: Clomifene, drug, voltammetry, pharmaceutical formulations. 1. INTRODUCTION An alkenyl group containing molecules play a vital role in drug chemistry.1 There are innumerable chemical reactions that involve or produce a carbon-carbon double bond group as an intermediate or as an end produce.1 Consequently the discovery of the first non-steroidal antiestrogen, several studies have been conducted to determine the mechanism of Corresponding author * action of this classes of compounds.
    [Show full text]
  • Supplementary Methods
    1 Supplementary Methods Definitions of the reproductive traits used in the analysis Reproductive trait Definition Age at first birth (years) Age at first live birth (females only). Age at last birth (years) Age at last live birth (females only). Age at menarche (years) Age at menarche between 9 and 17 years. Age at natural menopause (years) Age at last menstrual period excluding those with surgical menopause or taking hormone replacement therapy. Bilateral oophorectomy Ever had bilateral oophorectomy (case) vs. never (control). Breast cancer Breast cancer on registry (ICD10 C50, ICD9 174&175), vs no cancer reported (control). Dysmenorrhea Dysmenorrhea listed as an illness (reported at interview). Early menarche Youngest 5% of BMI adjusted age at menarche(case) vs oldest 5% (control). Age at menarche defined as above. Early menopause Age at natural menopause (as defined above) at 20-45 years (case) vs. 50-60 years (control). Endometrial cancer Endometrial cancer on registry (ICD10 C54, ICD9 182) vs no cancer reported. Endometriosis Endometriosis listed as an illness (reported at interview). Fibroids Fibroids listed as an illness (reported at interview). Hysterectomy Ever had hysterectomy (case) vs. never (control). Irregular menstrual cycles Women still menstruating reporting irregular cycles (case) vs. regular cycles (control). Length of menstrual cycle (days) Women still menstruating reporting regular cycles. Excludes women taking oral contraceptives, HRT or hormone medications (see list below) and pregnant women. Long menstrual cycle (vs average) Length of menstrual cycle >31 days (case) vs 28 days (control). As defined above. Menopausal symptoms Menopausal symptoms listed as an illness (reported at interview). Menorrhagia Menorrhagia listed as an illness (reported at interview).
    [Show full text]
  • In Vitro and in Silico Analyses of the Inhibition of Human Aldehyde Oxidase By
    JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 In Vitro and In Silico Analyses of the Inhibition of Human Aldehyde Oxidase by Bazedoxifene, Lasofoxifene, and Structural Analogues Shiyan Chen, Karl Austin-Muttitt, Linghua Harris Zhang, Jonathan G.L. Mullins, and Aik Jiang Lau Downloaded from Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore jpet.aspetjournals.org (S.C., A.J.L.); Institute of Life Science, Swansea University Medical School, United Kingdom (K.A-M, J.G.L.M.); NanoBioTec, LLC., Whippany, New Jersey, U.S.A. (L.H.Z.); at ASPET Journals on September 29, 2021 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (A.J.L.) 1 JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 Running Title In Vitro and In Silico Analyses of AOX Inhibition by SERMs Corresponding author: Dr. Aik Jiang Lau Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. Downloaded from Tel.: 65-6601 3470, Fax: 65-6779 1554; E-mail: [email protected] jpet.aspetjournals.org Number of text pages: 35 Number of tables: 4 Number of figures: 8 at ASPET Journals on September 29, 2021 Number of references 60 Number of words in Abstract (maximum
    [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]