Treprostinil (original) (raw)

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Chemical compound

Treprostinil
Clinical data
Trade names Remodulin, Orenitram, Tyvaso, others
AHFS/Drugs.com Monograph
License data US DailyMed: Treprostinil
Pregnancy category AU: B3
Routes of administration Subcutaneous, intravenous, inhalation, by mouth
ATC code B01AC21 (WHO)
Legal status
Legal status US: ℞-only[1][2][3][4] EU: Rx-only[5] In general: ℞ (Prescription only)
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
IUPAC name (1_R_,2_R_,3a_S_,9a_S_)-[[2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3_S_)-3-hydroxyoctyl]-1_H_-benz[f]inden-5-yl]oxy]acetic acid
CAS Number 81846-19-7 ☒N
PubChem CID 6918140
IUPHAR/BPS 5820
DrugBank DB00374 checkY
ChemSpider 5293353 checkY
UNII RUM6K67ESG
KEGG D06213 ☒ND08628 ☒N
ChEBI CHEBI:50861 checkY
ChEMBL ChEMBL1201254 ☒N
CompTox Dashboard (EPA) DTXSID901021654 Edit this at Wikidata
ECHA InfoCard 100.236.149 Edit this at Wikidata
Chemical and physical data
Formula C23H34O5
Molar mass 390.520 g·mol−1
InChI 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 checkYKey:PAJMKGZZBBTTOY-ZFORQUDYSA-N checkY
☒NcheckY (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]

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

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]

Common side effects depending on route of administration:

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

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

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

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]

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

  1. ^ a b c d "Remodulin- treprostinil injection, solution; Sterile diluent for remodulin- water injection, solution". DailyMed. 9 October 2023. Retrieved 21 May 2024.
  2. ^ a b "Orenitram- treprostinil tablet, extended release; Orenitram- treprostinil kit". DailyMed. 7 November 2023. Retrieved 21 May 2024.
  3. ^ a b "Tyvaso- treprostinil inhalant". DailyMed. 8 December 2023. Retrieved 21 May 2024.
  4. ^ a b "Tyvaso DPI- treprostinil inhalant; Tyvaso DPI- treprostinil kit". DailyMed. 26 January 2024. Retrieved 21 May 2024.
  5. ^ a b "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. ^ a b "Drug Approval Package: Remodulin (Treprostinil Sodium) NDA #021272". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
  8. ^ a b c d 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.