DOCSLIB.ORG

Full Text In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Return to October 2000 Table of Contents ORIGINAL ARTICLE Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers Michael Davidson, MD Drs. Davidson and Maki are with the Chicago Center for Ashok Marwah, PhD Clinical Research, Chicago, Ill.; Drs. A. Marwah, P. Marwah and Lardy are with the Institute for Enzyme Ronald J. Sawchuk, PhD Research and Department of Biochemistry, University of Kevin Maki, PhD Wisconsin, Madison, Wisc.; Dr. Sawchuk is with the Department of Pharmaceutics, College of Pharmacy, Padma Marwah, PhD University of Minnesota, Minneapolis, Minn.; and Dr. Charles Weeks, PhD Weeks is with Humanetics Corp., Chanhassen, Minn. Henry Lardy, PhD Medical subject headings: dehydroepiandrosterone sulfate; pharmacokinetics; prasterone; randomized controlled trials; steroids (Original manuscript submitted Apr. 17, 2000; received in revised form July 10, 2000 accepted July 10, 2000) Clin Invest Med 2000;23(5):300-10. © 2000 Canadian Medical Association Abstract the normal range. No changes in vital signs, blood chem- istry or urinalysis occurred during treatment with 3ß- Objectives: To evaluate the safety and pharmacokinetics acetyl-7-oxo-DHEA compared to placebo. The adminis- of 3-acetyl-7-oxo-DHEA (3ß-acetoxyandrost-5-ene- tered steroid was not detected in the blood but was rapid- 7,17-dione) given orally. ly converted to 7-oxo-DHEA-S, the concentrations of Design: A randomized, double blind, placebo-controlled, which were proportional to dose. This steroid sulfate did escalating dose study. not accumulate; plasma concentrations 12 hours after the Setting: The Chicago Center for Clinical Research. 3ß-acetyl-7-oxo-DHEA dose at 7 and 28 days on the 200 Participants: Twenty-two healthy men. mg/d dose were 15.8 and 16.3 mg/L respectively. The Study method: The participants received placebo (n = 6) mean time to peak plasma level of 7-oxo-DHEA-S was or 3-acetyl-7-oxo-DHEA (n = 16) at 50 mg/d for 7 days 2.2 hours; the mean half life was 2.17 hours. The appar- followed by a 7-day washout; 100 mg/d for 7 days fol- ent clearance averaged 172 L/h, and the apparent mean lowed by a 7-day washout; and 200 mg/d for 28 days. volume of distribution was 540 L. Outcome measures: Safety parameters, evaluated at Conclusion: These results indicate that 3ß-acetyl-7-oxo- each dose level, included measurement of total testos- DHEA is safe and well tolerated in normal healthy men terone, free testosterone, dihydrotestosterone, estradiol, at doses up to 200 mg/d for 4 weeks. cortisol, thyroxin and insulin levels. Analyses for 7-oxo- DHEA-3ß-sulfate (DHEA-S), the only detectable meta- bolic product of the administered steroid, were conduct- Résumé ed on plasma drawn from all subjects at 0.25, 0.5, 1, 2, 4, 6 and 12 hours after the final 100 mg dose of 3ß-acetyl- Objectifs : Évaluer l’innocuité et la pharmacocinétique 7-oxo-DHEA. de la 3-acétyl-7-oxo-DHEA (3ß-acétoxyandrost-5-ène- Results: There were no differences in the clinical labora- 7,17-dione) administrée par voie orale. tory values or in reported minor adverse experiences, Conception : Étude randomisée, à double insu, contrôlée between treatment and placebo groups. In general, blood par placebo et à dose croissante. hormone concentrations were unaffected by the treat- Contexte : Le Chicago Center for Clinical Research. ment with 3ß-acetyl-7-oxo-DHEA and remained within Participants : Vingt-deux hommes en bonne santé. 300 Clin Invest Med • Vol 23, no 5, octobre 2000 3-acetyl-7-oxo-dehydroepiandrosterone in healthy men Méthode d’étude : Les participants ont reçu un placebo demeurées à l’intérieur de la plage normale. Les signes (n = 6) ou de la 3-acétyl-7-oxo-DHEA (n = 16) à raison vitaux, la chimie sanguine ou les résultats d’analyses de 50 mg/j pendant 7 jours, suivis d’une période d’élim- d’urine au cours du traitement à la 3b-acétyl-7-oxo- ination de 7 jours, de 100 mg/j pendant 7 jours, suivis DHEA n’ont pas changé comparativement à ceux des d’une période d’élimination de 7 jours, et de 200 mg/j sujets qui ont reçu le placebo. On n’a pas détecté le pendant 28 jours. stéroïde administré dans le sang, mais il a été converti Mesures de résultats : Les paramètres d’innocuité éval- rapidement en 7-oxo-DHEA-S, dont les concentrations ués dans le cas de chaque dose ont inclus la mesure des ont été proportionnelles à la dose. Ce sulfate de stéroïde taux de testostérone totale, de testostérone libre, de dihy- ne s’est pas accumulé. Les concentrations plasmatiques drotestostérone, d’estradiol, de cortisol, de thyroxine et 12 heures après la dose de 3b-acétyl-7-oxo-DHEA à 7 et d’insuline. Le plasma prélevé chez tous les sujets 0,25, 0,5, 28 jours chez les sujets qui ont reçu la dose de 200 mg/j 1, 2, 4, 6 et 12 heures après la dernière dose de 100 mg de ont été de 15,8 et 16,3 mg/L respectivement. Il a fallu en 3b-acétyl-7-oxo-DHEA a été soumis à des analyses de moyenne 2,2 heures pour que le taux plasmatique de 7- dépistage du 7-oxo-DHEA-3b-sulfate (DHEA-S), le seul oxo-DHEA-S atteigne son maximum et la demi-vie produit métabolique détectable du stéroïde administré. moyenne a été de 2,17 heures. La clairance apparente Résultats : On n’a enregistré aucune différence entre les s’est établie en moyenne à 172 L/h et le volume moyen résultats d’analyses cliniques ou les expériences indésir- apparent de distribution s’est établi à 540 L. ables mineures déclarées chez les sujets traités par rap- Conclusion : Ces résultats indiquent que la 3b-acétyl-7- port à ceux qui ont reçu un placebo. En général, les con- oxo-DHEA est sans danger et bien tolérée chez les centrations d’hormones dans le sang n’ont pas été affec- hommes normaux en bonne santé à des doses qui peuvent tées par le traitement à la 3b-acétyl-7-oxo-DHEA et sont atteindre 200 mg/j pendant 4 semaines. Introduction particularly in the aged, is suggested to improve with DH E A su p p l e m e n t a t i o n , 7– 1 3 with possible benefits in Dehydroepiandrosterone (DHEA) is a steroid pro- muscle strength, mood ratings and memory perfor- duced by the adrenal cortex in response to stimula- mance. tion by adrenocorticotropin (ACTH)1, 2 and in the Several adverse experiences have been reported brain by pathways still to be elucidated.3 Most of the from the use of DHEA.12 , 1 4 Some involve alterations circulating DHEA is in its conjugated form, dehy- of sex hormone levels, resulting from transformation droepiandrosterone sulfate (DHEA-S), the most of DHEA to testosterone and estrogen.11, 1 5 Th e s e abundant steroid in human blood.1 Normal levels of steroid transformations may lead to acne, hair loss, DHEA-S vary with age; levels are high in the devel- facial hirsutism, mood changes, deepening of the oping fetus, nearly undetectable shortly after birth, voice and other signs of masculinization. DHEA ma y rise at adrenarch, peak at about age 25 years and then also affect the growth of prostate cancer in men and gradually decline.4, 5 On average, by age 75 years, breast cancer in women; the National Institute of circulating DHEA-S levels are only about 10% of Aging has issued a public service announcement their peak concentration. warning consumers about the use of DHEA be c a u s e Until the late 1970s, DHEA was considered a rela- of its sex steroid-associated side effe c t s . 16 tively inert compound whose main function was as There is need for a DHEA-like compound capable an intermediate in the bioconversion of cholesterol to of similar health maintenance benefits without the androgens and estrogens. Pioneering studies2, 6 st i m u - adverse effects. Fluasterone, a fluorinated form of lated research, which indicated that DHEAhas poten- DHEA, avoids the androgen-producing effects of tial benefits in treating a number of conditions, DH E A and is being developed as a drug. Another can- including systemic lupus erythematosus, cancer, didate is the natural metabolite, 7-oxo-DHEA wh i c h insulin resistance, cardiovascular disease, viral infec- is produced from DHEA via the 7a -hydroxy deriva- tions, osteoporosis and depression.7– 1 3 Because levels tive followed by its oxidation. 7-oxo-DHEA does not of DHEA and general health decline with age, it has activate the androgen receptor,17 is not converted to been postulated that DHEA replacement may help to an d r o g e n 18 and because of its carbonyl function on the maintain a more youthful state. Overall wellbeing, 7 position is not a substrate for the estroge n - f o r m i n g Clin Invest Med • Vol 23, no 5, October 2000 301 Davidson et al Metabolic functions of 7-oxo-dehydroepiandrosterone Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S) are produced in human adrenal glands beginning at about 7 years of age (adrenarche). DHEA-S is the most abundant steroid (14 mg/L) in the blood plasma of humans at age 20 to 30 years and decreases steadily to about one-tenth that con- centration at age 70 to 80 years. DHEA is an intermediate in the biologic conversion of cholesterol to androgens and estrogens.
Recommended publications
  • DHEA | Medchemexpress

    DHEA | Medchemexpress

    Inhibitors Product Data Sheet DHEA • Agonists Cat. No.: HY-14650 CAS No.: 53-43-0 Molecular Formula: C₁₉H₂₈O₂ • Molecular Weight: 288.42 Screening Libraries Target: Androgen Receptor; Endogenous Metabolite Pathway: Others; Metabolic Enzyme/Protease Storage: Please store the product under the recommended conditions in the Certificate of Analysis. SOLVENT & SOLUBILITY In Vitro DMSO : 50 mg/mL (173.36 mM; Need ultrasonic) Ethanol : 50 mg/mL (173.36 mM; Need ultrasonic) H2O : 1 mg/mL (3.47 mM; Need ultrasonic) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 3.4672 mL 17.3358 mL 34.6717 mL Stock Solutions 5 mM 0.6934 mL 3.4672 mL 6.9343 mL 10 mM 0.3467 mL 1.7336 mL 3.4672 mL Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: Cremophor EL Solubility: 14.29 mg/mL (49.55 mM); Clear solution; Need ultrasonic 2. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 3. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 4. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 5. Add each solvent one by one: 10% EtOH >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (8.67 mM); Clear solution 6.
  • 16A-Fluoro-5-Androsten-17-0Ne

    16A-Fluoro-5-Androsten-17-0Ne

    MILITARY MEDICINE, 167, Suppl. 1:060,2002 Inhibition of Adjuvant-Induced Arthritis by 16a-Fluoro-5-Androsten-17-0ne Guarantor: Arthur G. Schwartz, PhD Contributors: Arthur G. Schwartz, PhD; Laura L. Pashko, PhD The adrenal steroid dehydroepiandrosterone (DHEA) produces tant receptor and that inhibition ofthis enzyme by DHEA me­ cancer-preventive, antiatherosclerotic, antidiabetic, Immuno­ diates some of the biological effects of the steroid. DHEA is a modulating, and anti-inflammatory effects in laboratory ani­ potent uncompetitive inhibitor of G6PDH, the rate-controlling mals. The clinical use of DHEAis limited by its androgenicity. Downloaded from https://academic.oup.com/milmed/article/167/suppl_1/60/4820113 by guest on 01 October 2021 enzyme in thepentose phosphate pathway, 10 and it appearsthat Wehave developed a synthetic congener ofDHEAcalled fluaster­ the antiproliferative and antitumor-promoting effects of the one that, in animal tests, lacks the androgenicity, estrogenicity, and peroxisome-proliferating effects of DHEA but retains the DHEA class of steroids is mediated through inhibition of cancer-preventive, antidiabetic, and anti-inflammatory efficacy. G6PDH.1,11,12 Two important metabolic consequences ofG6PDH This report discusses how fluasterone ameliorates the develop­ inhibition are a lowering ofNADPH-reducing equivalents avail­ ment of joint inflammation in an adjuvant-arthritis model in able forbiosynthetic processes, including ribo- and deoxyribo­ Lewis rats. nucleotide synthesis, and a reduction in ribose-5-phosphate,
  • Us Anti-Doping Agency

    Us Anti-Doping Agency

    2019U.S. ANTI-DOPING AGENCY WALLET CARDEXAMPLES OF PROHIBITED AND PERMITTED SUBSTANCES AND METHODS Effective Jan. 1 – Dec. 31, 2019 CATEGORIES OF SUBSTANCES PROHIBITED AT ALL TIMES (IN AND OUT-OF-COMPETITION) • Non-Approved Substances: investigational drugs and pharmaceuticals with no approval by a governmental regulatory health authority for human therapeutic use. • Anabolic Agents: androstenediol, androstenedione, bolasterone, boldenone, clenbuterol, danazol, desoxymethyltestosterone (madol), dehydrochlormethyltestosterone (DHCMT), Prasterone (dehydroepiandrosterone, DHEA , Intrarosa) and its prohormones, drostanolone, epitestosterone, methasterone, methyl-1-testosterone, methyltestosterone (Covaryx, EEMT, Est Estrogens-methyltest DS, Methitest), nandrolone, oxandrolone, prostanozol, Selective Androgen Receptor Modulators (enobosarm, (ostarine, MK-2866), andarine, LGD-4033, RAD-140). stanozolol, testosterone and its metabolites or isomers (Androgel), THG, tibolone, trenbolone, zeranol, zilpaterol, and similar substances. • Beta-2 Agonists: All selective and non-selective beta-2 agonists, including all optical isomers, are prohibited. Most inhaled beta-2 agonists are prohibited, including arformoterol (Brovana), fenoterol, higenamine (norcoclaurine, Tinospora crispa), indacaterol (Arcapta), levalbuterol (Xopenex), metaproternol (Alupent), orciprenaline, olodaterol (Striverdi), pirbuterol (Maxair), terbutaline (Brethaire), vilanterol (Breo). The only exceptions are albuterol, formoterol, and salmeterol by a metered-dose inhaler when used
  • Effects of Aminoglutethimide on A5-Androstenediol Metabolism in Postmenopausal Women with Breast Cancer1

    Effects of Aminoglutethimide on A5-Androstenediol Metabolism in Postmenopausal Women with Breast Cancer1

    [CANCER RESEARCH 42, 4797-4800, November 1982] 0008-5472/82/0042-0000802.00 Effects of Aminoglutethimide on A5-Androstenediol Metabolism in Postmenopausal Women with Breast Cancer1 Charles E. Bird,2 Valerie Masters, Ernest E. Sterns, and Albert F. Clark Departments of Medicine [C. E. B., V. M.], Surgery [E. E. S.J, and Biochemistry [A. F. C.], Queen s University and Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7 ABSTRACT women. More recently, we (8) and others (18) reported that the production of A5-androstene-3/8,17/8-diol in normal post- A5-Androstene-3/8,1 7/S-diol has potential estrogenic activity menopausal women is approximately 500 to 700 fig/24 hr. because it is known to bind to receptors and translocate to the AG, in combination with hydrocortisone, has been utilized to nucleus of certain estrogen target tissues. Its role in the biology inhibit estrogen production in patients with breast cancer (21 ). of breast cancer is unclear. Aminoglutethimide plus hydrocor This form of therapy has been termed "medical adrenalec tisone ("medical adrenalectomy") has been used to treat post- tomy," and studies suggest that it is as effective as surgical menopausal women with metastatic breast cancer. adrenalectomy. The hydrocortisone shuts off the basal adre- We studied A5-androstene-3/3,17/?-diol metabolism in post- nocortical production of estrogen precursors; AG not only menopausal women with breast cancer before and during slows down steroid biosynthesis at an early step but also aminoglutethimide-plus-hydrocortisone therapy, utilizing the specifically inhibits the aromatization of A4-androstenedione to constant infusion technique.
  • WO 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT

    WO 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT

    (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 WO 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT (51) International Patent Classification: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, CI2Q 1/32 (2006.01) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (21) International Application Number: EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, PCT/US2018/021 109 MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (22) International Filing Date: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 06 March 2018 (06.03.2018) KM, ML, MR, NE, SN, TD, TG). (25) Filing Language: English Declarations under Rule 4.17: (26) Publication Langi English — as to applicant's entitlement to apply for and be granted a patent (Rule 4.1 7(H)) (30) Priority Data: — as to the applicant's entitlement to claim the priority of the 62/484,141 11 April 2017 ( 11.04.2017) US earlier application (Rule 4.17(Hi)) (71) Applicant: REGENERON PHARMACEUTICALS, Published: INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, — with international search report (Art. 21(3)) New York 10591-6707 (US). — with sequence listing part of description (Rule 5.2(a)) (72) Inventors: STEVIS, Panayiotis; 777 Old Saw Mill Riv er Road, Tarrytown, New York 10591-6707 (US).
  • Sex Hormone-Binding Globulin (SHBG) As an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome

    Sex Hormone-Binding Globulin (SHBG) As an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome

    International Journal of Molecular Sciences Review Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome Xianqin Qu 1,* and Richard Donnelly 2 1 School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia 2 School of Medicine, University of Nottingham, Derby DE22 3DT, UK; [email protected] * Correspondence: [email protected]; Tel.: +61-2-95147852 Received: 1 October 2020; Accepted: 28 October 2020; Published: 1 November 2020 Abstract: Human sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver that binds sex steroids with high affinity and specificity. Clinical observations and reports in the literature have suggested a negative correlation between circulating SHBG levels and markers of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Decreased SHBG levels increase the bioavailability of androgens, which in turn leads to progression of ovarian pathology, anovulation and the phenotypic characteristics of polycystic ovarian syndrome (PCOS). This review will use a case report to illustrate the inter-relationships between SHBG, NAFLD and PCOS. In particular, we will review the evidence that low hepatic SHBG production may be a key step in the pathogenesis of PCOS. Furthermore, there is emerging evidence that serum SHBG levels may be useful as a diagnostic biomarker and therapeutic target for managing women with PCOS. Keywords: adolescents; hepatic lipogenesis; human sex hormone-binding globulin; insulin resistance; non-alcoholic fatty liver disease; polycystic ovary syndrome 1. Introduction Polycystic ovary syndrome (PCOS) is a complex, common reproductive and endocrine disorder affecting up to 10% of reproductive-aged women [1].
  • In Human Prostate Cancer Cells (Ara70͞hydroxyflutamide͞casodex͞testosterone͞7-Oxo-DHEA)

    In Human Prostate Cancer Cells (Ara70͞hydroxyflutamide͞casodex͞testosterone͞7-Oxo-DHEA)

    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 11083–11088, September 1998 Biochemistry D5-Androstenediol is a natural hormone with androgenic activity in human prostate cancer cells (ARA70yhydroxyflutamideycasodexytestosteroney7-oxo-DHEA) HIROSHI MIYAMOTO*, SHUYUAN YEH*, HENRY LARDY†,EDWARD MESSING*, AND CHAWNSHANG CHANG*†‡ *George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642; and †Institute for Enzyme Research and Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792 Contributed by Henry Lardy, July 29, 1998 ABSTRACT It is known that androst-5-ene-3b,17b-diol presence of AR and ARA70. Our results suggest that Adiol (Adiol), a precursor of testosterone (T), can activate estrogen itself can activate AR transcriptional activity in human pros- target genes. The androgenic activity of Adiol itself, however, tate cancer cells, and that ARA70 can further enhance Adiol- is poorly understood. Using a transient transfection assay, we mediated activation of the AR. here demonstrate in human prostate cancer cells that Adiol can activate androgen receptor (AR) target genes in the MATERIALS AND METHODS presence of AR, and that AR coactivator ARA70 can further enhance this Adiol-induced AR transcriptional activity. In Chemicals and Plasmids. Adiol, DHEA, androst-5-ene- contrast to this finding, an active metabolite of dehydroepi- 7,17-dione (Adione), T, DHT, and E2 were purchased from androsterone, 7-oxo-dehydroepiandrosterone, does not acti- Sigma, 7-oxo-DHEA was synthesized from DHEA as de- vate AR target gene in the absence or presence of ARA70. Thin scribed (9), trilostane was provided by T.-M.
  • Cyclodextrins As Drug Carrier Molecule: a Review

    Cyclodextrins As Drug Carrier Molecule: a Review

    Sci Pharm www.scipharm.at Review Open Access Cyclodextrins as Drug Carrier Molecule: A Review ARUN RASHEED *, ASHOK KUMAR C. K., SRAVANTHI V. V. N. S. S. Department of Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Sri Sainath Nagar, Tirupati, Andhra Pradesh, India-517502 * Corresponding author. E-mail: [email protected] (R. Arun) Sci Pharm. 2008; 76: 567–598 doi:10.3797/scipharm.0808-05 Published: November 1st 2008 Received: August 5th 2008 Accepted: October 31st 2008 This article is available from: http://dx.doi.org/10.3797/scipharm.0808-05 © Arun et al; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. The most common pharmaceutical application of cyclodextrin is to enhance the solubility, stability, safety and bioavailability of drug molecules. The purpose of this review is to discuss and summarize some of the findings and applications of cyclodextrin (CD) and their derivatives in different areas of drug delivery. This article highlights the molecular structure, properties like complexation, solubility etc. of cyclodextrins and focuses on its use for parenteral, oral, ophthalmic and nasal drug delivery. Other routes including dermal, rectal, sublingual and pulmonary delivery are also briefly addressed. The objective of this contribution is to focus on the potential use of chemically modified cyclodextrins as high-performance drug carriers in drug delivery systems with emphasis on the more recent developments.
  • An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis

    An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis

    0022-3565/09/3293-1100–1109$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 329, No. 3 Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics 145086/3474987 JPET 329:1100–1109, 2009 Printed in U.S.A. An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis Halina Offner, Gary S. Firestein, David L. Boyle, Raymond Pieters, James M. Frincke, Armando Garsd, Steven K. White, Christopher L. Reading, and Dominick L. Auci Department of Neurology, Oregon Health and Science University, Portland, Oregon (H.O.); Institute for Risk Assessment Sciences-Immunotoxicology, Utrecht University, Utrecht, The Netherlands (R.P.); Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, California (D.L.B., G.S.F.); and Hollis-Eden Pharmaceuticals Inc., San Diego, California (J.M.F., A.G., S.K.W., C.L.R., D.L.A.) Downloaded from Received August 20, 2008; accepted March 17, 2009 ABSTRACT Dehydroepiandrosterone (DHEA) treatment provides diverse anti- even when treatments were delayed until 7 days after the onset jpet.aspetjournals.org inflammatory benefits in rodent models of diseases, including of arthritis. Furthermore, dose-dependent benefit was observed rheumatoid arthritis (RA), but only limited benefits to patients. In in the DBA mouse model of collagen antibody-induced arthritis, rodents, DHEA is metabolized to (among others) androstene- as well as reductions in IL-6 and matrix metalloproteinase-3 3␤,7␤,17␤-triol (AET), which retains potent anti-inflammatory mRNA levels in joints at the peak of disease and at the end of activity.
  • Appendix B Banned Drugs

    Appendix B Banned Drugs

    APPENDIX B BANNED DRUGS (This list complies with 2004-2005 NCAA Bylaw 31.2.3.1 Banned Drugs) A. Stimulants: amiphenazole amphetamine bemigride benzphetamine bromantan caffeine1 (guarana) chlorphentermine cocaine cropropamide crothetamide diethylpropion dimethylamphetamine doxapram ephedrine (ephedra, ma huang) ethamivan ethylamphetamine fencamfamine meclofenoxate methamphetamine methylene-dioxymethamphetamine [MDMA (ecstasy)] methylphenidate nikethamide pemoline pentetrazol phendimetrazine phenmetrazine phentermine phenylephrine phenylpropanolamine (ppa) picrotoxine pipradol prolintane strychnine synephrine (citrus aurantium, zhi shi, bitter orange) and related compounds Approved by Cabinet:1/31/05 Adopted by Board of Trustees:3/18/05 Page 12 of 15 B. Anabolic Agents: polythiazide anabolic steroids quinethazone androstenediol spironolactone androstenedione triamterene boldenone trichlormethiazide clostebol and related compounds dehydrochlormethyltestosterone dehydroepiandrosterone (DHEA) dihydrotestosterone (DHT) D. Street Drugs: dromostanolone heroin fluoxymesterone marijuana3 gestrinone THC mesterolone (tetrahydrocannabinol3 methandienone methenolone methyltestosterone nandrolone norandrostenediol norandrostenedione norethandrolone oxandrolone oxymesterone oxymetholone stanozolol testosterone2 tetrahydrogestrinone (THG) trenbolone and related compounds other anabolic agents clenbuterol C. Diuretics: acetazolamide bendroflumethiazide benzthiazide bumetanide chlorothiazide chlorthalidone ethacrynic acid flumethiazide furosemide hydrochlorothiazide
  • The Effects of 5-Androstenediol in Androgen-Dependent Prostate

    The Effects of 5-Androstenediol in Androgen-Dependent Prostate

    Characterization of Value Nutrition’s 5-Androstenediol Product and its Proliferative Effects on the LNCaP Cell Line A Thesis Submitted to the Faculty of Worcester Polytechnic Institute in partial fulfillment of the requirements for the Degree of Master of Science in Biology and Biotechnology by _______________________________ Jaime L. Grouf October 2007 APPROVED: Jill Rulfs, Ph.D., Major Advisor ________________________________ Theodore Crusberg, Committee Member ________________________________ JoAnn Whitefleet-Smith, Committee Member ________________________________ TABLE OF CONTENTS TABLE OF CONTENTS............................................................................................................................. 2 ABSTRACT .................................................................................................................................................. 3 ACKNOWLEDGEMENTS ......................................................................................................................... 5 DEDICATION.............................................................................................................................................. 6 INTRODUCTION........................................................................................................................................ 7 PROSTATE CANCER .................................................................................................................................. 7 PHYSIOLOGICAL ROLE OF ANDROGENS IN THE PROSTATE ...................................................................
  • (12) United States Patent (10) Patent No.: US 8,383,154 B2 Bar-Shalom Et Al

    (12) United States Patent (10) Patent No.: US 8,383,154 B2 Bar-Shalom Et Al

    USOO8383154B2 (12) United States Patent (10) Patent No.: US 8,383,154 B2 Bar-Shalom et al. (45) Date of Patent: Feb. 26, 2013 (54) SWELLABLE DOSAGE FORM COMPRISING W W 2.3. A. 3. 2. GELLAN GUMI WO WOO1,76610 10, 2001 WO WOO2,46571 A2 6, 2002 (75) Inventors: Daniel Bar-Shalom, Kokkedal (DK); WO WO O2/49571 A2 6, 2002 Lillian Slot, Virum (DK); Gina Fischer, WO WO 03/043638 A1 5, 2003 yerlosea (DK), Pernille Heyrup WO WO 2004/096906 A1 11, 2004 Hemmingsen, Bagsvaerd (DK) WO WO 2005/007074 1, 2005 WO WO 2005/007074 A 1, 2005 (73) Assignee: Egalet A/S, Vaerlose (DK) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 JECFA, “Gellangum”. FNP 52 Addendum 4 (1996).* U.S.C. 154(b) by 1259 days. JECFA, “Talc”, FNP 52 Addendum 1 (1992).* Alterna LLC, “ElixSure, Allergy Formula', description and label (21) Appl. No.: 111596,123 directions, online (Feb. 6, 2007). Hagerström, H., “Polymer gels as pharmaceutical dosage forms'. (22) PCT Filed: May 11, 2005 comprehensive Summaries of Uppsala dissertations from the faculty of pharmacy, vol. 293 Uppsala (2003). (86). PCT No.: PCT/DK2OOS/OOO317 Lin, “Gellan Gum', U.S. Food and Drug Administration, www. inchem.org, online (Jan. 17, 2005). S371 (c)(1), Miyazaki, S., et al., “In situ-gelling gellan formulations as vehicles (2), (4) Date: Aug. 14, 2007 for oral drug delivery”. J. Control Release, vol. 60, pp. 287-295 (1999). (87) PCT Pub. No.: WO2005/107713 Rowe, Raymond C.