Tolvaptan

Tolvaptan (trade names Samsca, Jinarc, and others) is an aquaretic drug that functions as a selective, competitive vasopressin receptor 2 (V2) antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca.

Tolvaptan
Clinical data
Trade namesSamsca, Jinarc, Jynarque
Other namesOPC-41061
AHFS/Drugs.comMonograph
MedlinePlusa609033
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    BioavailabilityUnknown (40% absorbed)
    Protein binding99%
    MetabolismHepatic (CYP3A4-mediated)[1]
    Elimination half-life12 hours (terminal)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.219.212
    Chemical and physical data
    FormulaC26H25ClN2O3
    Molar mass448.95 g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    The FDA granted tolvaptan a fast-track designation for clinical trials investigating its use for the treatment of polycystic kidney disease.[2]

    Side effects

    The FDA has determined that tolvaptan should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially leading to liver failure.[3] When using to treat hyponatremia, it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome.[4]

    Pharmacology

    Tolvaptan is a selective V2 receptor antagonist.[5]

    Chemistry

    Tolvaptan is a racemate, a 1:1 mixture of the following two enantiomers:[6]

    Enantiomers of tolvaptan

    (R)-Tolvaptan
    CAS number: 331947-66-1
    (S)-Tolvaptan
    CAS number: 331947-44-5

    References
    1. Shoaf S, Elizari M, Wang Z, et al. (2005). "Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias". J Cardiovasc Pharmacol Ther. 10 (3): 165–71. doi:10.1177/107424840501000304. PMID 16211205.
    2. "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Medical News Today. Healthline Media UK Ltd. Retrieved 6 December 2018.
    3. "U.S. Food and Drug Administration." Samsca (Tolvaptan): Drug Safety Communication. N.p., 30 Apr. 2013. Web. 1 June 2014. <http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm>
    4. Goodman & Gilman's the pharmacological basis of therapeutics. Brunton, Laurence L, Knollmann, Björn C, Hilal-Dandan, Randa (Thirteenth ed.). New York. ISBN 9781259584732. OCLC 994570810.CS1 maint: others (link)
    5. "SAMSCA (tolvaptan) tablets - Package Insert" (PDF). Otsuka Pharmaceutical Co., Ltd. Retrieved 6 December 2018.
    6. Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 222.
    • Gheorghiade M, Niazi I, Ouyang J, et al. (2003). "Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial". Circulation. 107 (21): 2690–6. doi:10.1161/01.CIR.0000070422.41439.04. PMID 12742979.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.