Tolvaptan

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Tolvaptan
(RS)-Tolvaptan Structural Formula V1.svg
Tolvaptan ball-and-stick model.png
Clinical data
Trade namesSamsca, Jinarc, Jynarque
SynonymsOPC-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 Edit this at Wikidata
Chemical and physical data
FormulaC26H25ClN2O3
Molar mass448.95 g·mol−1
3D model (JSmol)
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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.

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

Side effects[edit]

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[edit]

Tolvaptan is a selective V2 receptor antagonist.[5]

Chemistry[edit]

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

Enantiomers of tolvaptan
(R)-Tolvaptan Structural Formula V1.svg
(R)-Tolvaptan
CAS number: 331947-66-1
(S)-Tolvaptan Structural Formula V1.svg
(S)-Tolvaptan
CAS number: 331947-44-5

References[edit]

  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.

External links[edit]

  • 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.