Treprostinil

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; EU: Rx-only; 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 (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	81846-19-7 ;
PubChem CID	6918140;
IUPHAR/BPS	5820;
DrugBank	DB00374 ;
ChemSpider	5293353 ;
UNII	RUM6K67ESG;
KEGG	D06213 ; D08628 ;
ChEBI	CHEBI:50861 ;
ChEMBL	ChEMBL1201254 ;
CompTox Dashboard (EPA)	DTXSID901021654 ;
ECHA InfoCard	100.236.149
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 ; Key:PAJMKGZZBBTTOY-ZFORQUDYSA-N ;
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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]

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

Since treprostinil is a vasodilator, its antihypertensive effect may be compounded by other medications that affect the blood pressure, including calcium channel blockers, diuretics, and other vasodilating agents.^[8]
Because of treprostinil's inhibiting effect on platelet aggregation, there is an increased risk of bleeding, especially among patients who are also taking anticoagulants.^[8]
It is not known whether treprostinil is excreted in breast milk. Caution is advised when administering this medication to nursing women.
Caution is advised when administering treprostinil to patients who have impaired kidney or liver function.^[8]

Common side effects depending on route of administration:

85% of patients report pain or other reaction at the infusion site.^[8]

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]

References

^ ^a ^b ^c ^d "Remodulin- treprostinil injection, solution; Sterile diluent for remodulin- water injection, solution". DailyMed. 9 October 2023. Retrieved 21 May 2024.
^ ^a ^b "Orenitram- treprostinil tablet, extended release; Orenitram- treprostinil kit". DailyMed. 7 November 2023. Retrieved 21 May 2024.
^ ^a ^b "Tyvaso- treprostinil inhalant". DailyMed. 8 December 2023. Retrieved 21 May 2024.
^ ^a ^b "Tyvaso DPI- treprostinil inhalant; Tyvaso DPI- treprostinil kit". DailyMed. 26 January 2024. Retrieved 21 May 2024.
^ ^a ^b "Trepulmix EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 9 April 2020.
^ 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.
^ ^a ^b "Drug Approval Package: Remodulin (Treprostinil Sodium) NDA #021272". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
^ ^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.
^ 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.
^ "Drug Approval Package: Remodulin". U.S. Food and Drug Administration (FDA). 7 February 2019. Retrieved 9 April 2020.
^ "Drug Approval Package: Tyvaso (Treprostinil) Inhalation Solution NDA #022387". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
^ "Drug Approval Package: Orenitram (Treprostinil) Extended Release Tablets NDA #203496". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 9 April 2020.
^ 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.