Treprostinil

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Treprostinil
Treprostinil.svg
Treprostinil2.png
Clinical data
Trade names Remodulin, Orenitram, Tyvaso, others
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:B3
Routes of
administration
Subcutaneous, intravenous, inhalation, by mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~100%
Metabolism Substantially metabolized by the liver
Elimination half-life 4 hours
Excretion Urine (79% of administered dose is excreted as 4% unchanged drug and 64% as identified metabolites); feces (13%)
Identifiers
  • (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.236.149 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H34O5
Molar mass 390.520 g·mol−1
  • InChI=1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1 Yes check.svgY
  • Key:PAJMKGZZBBTTOY-ZFORQUDYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. [6]

Contents

Treprostinil was approved for use in the United States in May 2002. [7]

Medical uses

Treprostinil is indicated for the treatment of pulmonary arterial hypertension in people with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. [1]

Adverse effects

Common side effects depending on route of administration:

Administration

For infusion

Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion. [1]

Inhaled form

The inhaled form of treprostinil was approved by the FDA in July 2009, and is sold under the brand name Tyvaso. [3] [4]

Oral form

The oral form of treprostinil was approved by the FDA in December 2013, and is sold under the brand name Orenitram. [2]

History

During the 1960s a UK research team, headed by Professor John Vane began to explore the role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons, Vane discovered that aspirin and other oral anti-inflammatory drugs worked by inhibiting the synthesis of prostaglandins. This finding opened the door to a broader understanding of the role of prostaglandins in the body.

Vane and a team from the Wellcome Foundation had identified a lipid mediator they called “PG-X,” which inhibited platelet aggregation. PG-X, which later would become known as prostacyclin, was 30 times more potent than any other known anti-aggregatory agent.[ citation needed ]

By 1976, Vane and fellow researcher Salvador Moncada published the first paper on prostacyclin, in the scientific journal Nature. [9]

Treprostinil (Remodulin) was approved for use in the United States in May 2002, [1] [7] and again in July 2018. [10] Tyvaso, the inhaled form of treprostinil, was approved for use in the United States in July 2009. [11] Orenitram was approved in December 2013. [12]

Treprostinil (Trepulmix) was approved for use in the European Union in April 2020. [5]

Research

Treprostinil therapy may be effective in treating Degos disease. [13]

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References

  1. 1 2 3 4 "Remodulin- treprostinil injection, solution; Sterile diluent for remodulin- water injection, solution". DailyMed. 9 October 2023. Retrieved 21 May 2024.
  2. 1 2 "Orenitram- treprostinil tablet, extended release; Orenitram- treprostinil kit". DailyMed. 7 November 2023. Retrieved 21 May 2024.
  3. 1 2 "Tyvaso- treprostinil inhalant". DailyMed. 8 December 2023. Retrieved 21 May 2024.
  4. 1 2 "Tyvaso DPI- treprostinil inhalant; Tyvaso DPI- treprostinil kit". DailyMed. 26 January 2024. Retrieved 21 May 2024.
  5. 1 2 "Trepulmix EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 9 April 2020.
  6. Torres F, Rubin LJ (January 2013). "Treprostinil for the treatment of pulmonary arterial hypertension". Expert Review of Cardiovascular Therapy. 11 (1): 13–25. doi:10.1586/erc.12.160. PMID   23259441. S2CID   29661141.
  7. 1 2 "Drug Approval Package: Remodulin (Treprostinil Sodium) NDA #021272". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
  8. 1 2 3 4 Kumar P, Thudium E, Laliberte K, Zaccardelli D, Nelsen A (December 2016). "A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration". Clinical Pharmacokinetics. 55 (12): 1495–1505. doi:10.1007/s40262-016-0409-0. PMC   5107196 . PMID   27286723.
  9. Moncada S, Gryglewski R, Bunting S, Vane JR (October 1976). "An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation". Nature. 263 (5579): 663–665. Bibcode:1976Natur.263..663M. doi:10.1038/263663a0. PMID   802670. S2CID   4279030.
  10. "Drug Approval Package: Remodulin". U.S. Food and Drug Administration (FDA). 7 February 2019. Retrieved 9 April 2020.
  11. "Drug Approval Package: Tyvaso (Treprostinil) Inhalation Solution NDA #022387". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
  12. "Drug Approval Package: Orenitram (Treprostinil) Extended Release Tablets NDA #203496". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
  13. Shapiro LS, Toledo-Garcia AE, Farrell JF (April 2013). "Effective treatment of malignant atrophic papulosis (Köhlmeier-Degos disease) with treprostinil--early experience". Orphanet Journal of Rare Diseases. 8: 52. doi: 10.1186/1750-1172-8-52 . PMC   3636001 . PMID   23557362.

Further reading