Prasugrel

Structural formula
1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Non-proprietary name	Prasugrel
other names	( RS ) - [5- [2-Cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -6,7-dihydro-4 H -thieno [3,2- c ] pyridin-2-yl] acetate ( IUPAC ) CS-747
Molecular formula	C 20 H 20 FNO 3 S
External identifiers / databases
CAS number 150322-43-3 (Prasugrel) 389574-19-0 (prasugrel hydrochloride) 1060616-79-6 (prasugrel hydrobromide) 1060616-84-3 (prasugrel mesylate) 389574-20-3 (Prasugrel maleate) 1191933-01-3 (Prasugrel hydrogen sulfate) 952340-40-8 (prasugrel benzenesulfonate) 1155404-76-4 (prasugrel p-toluenesulfonate) EC number 801-962-1 ECHA InfoCard 100.228.719 PubChem 6918456 ChemSpider 5293653 DrugBank DB06209 Wikidata Q416232
Drug information
ATC code	B01 AC22
Drug class	Antiplatelet drugs
properties
Molar mass	373.44 g mol −1
Melting point	120-121 ° C (racemate) 103 ° C (mesylate)
solubility	13 mg l −1 in water
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302-411 P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Prasugrel (development designations CS-747 , LY640315 ) is a platelet aggregation inhibitor from the group of thienopyridines , which prevents the formation of blood clots ( thrombi ). Prasugrel has been approved for use in acute coronary syndrome in the USA, England, Austria, Switzerland and Germany since 2009 . It thus represents an alternative to the active ingredient clopidogrel from the same group of active ingredients, which is currently still used in most cases in the therapy of heart attacks .

The medicinal product “Efient” (Europe) or “Effient” (USA) from Daiichi Sankyō and Eli Lilly and Company contains prasugrel · hydrochloride as the medicinal substance .

pharmacology

Like the other thienopyridines clopidogrel and ticlopidine, prasugrel is a prodrug that is converted into the active metabolite R-138727 in the body (by hydrolysis by esterases, followed by oxidation by the cytochrome P450 system ) . This seems to happen faster and to a greater extent than with the other substances in this group of drugs. Elimination occurs mainly through the kidneys.

The active metabolite binds to the P2Y ₁₂ - adenosine diphosphate receptor of the platelets . As a result, platelet activation via the glycoprotein IIb / IIIa receptor complex does not occur. Since the blockage of the P2Y ₁₂ receptor is irreversible, the platelets remain impaired throughout their lifespan. The blood does not fully clot until new platelets are formed over the course of five to seven days.

application areas

Prasugrel is used in combination with acetylsalicylic acid in patients with ST segment elevation myocardial infarction ( STEMI ) as part of treatment ( percutaneous transluminal coronary angioplasty ) during a cardiac catheter examination. In patients with non-ST segment elevation myocardial infarction (NSTEMI), early loading prior to the planned (next 48 hours) catheter treatment does not bring any benefit in terms of ischemic events (death from stroke or heart attack, emergency catheter treatment). However, the rate of bleeding complications increases, so that therapy should only be started as part of the heart catheter treatment.

In the phase 3 study on which the approval was based ( TRITON-TIMI 38 , a randomized, double-blind, multicenter study, n = 13,608), Prasugrel demonstrated the frequency of cardiovascular death (9.44% vs. 11.49%) for the primary endpoint , non-fatal myocardial infarction or non-fatal stroke, had a significantly greater benefit than clopidogrel. In contrast, bleeding occurred more frequently as a side effect (1.4%, vs. 0.9% in the clopidogrel group, of which 0.4% vs. 0.1% was fatal). The overall mortality therefore did not differ.

The German Institute for Quality and Efficiency in Health Care (IQWiG) does not assess the data situation as evidence, but merely as an indication of an advantage of prasugrel over clopidogrel. The study design of the TRITON study has been criticized as it may favor prasugrel. The increased rate of side effects, especially bleeding, is also emphasized.

For regional anesthesia procedures close to the spinal cord ( spinal anesthesia or epidural anesthesia ), Prasugrel should be discontinued 7–10 days in advance and used again at least six hours after the procedure.

Individual evidence

1. ↑ Xianhua Pan, Rui Huang, Jianshui Zhang, Liping Ding, Weijin Li, Qunhui Zhang, Feng Liu: Efficient synthesis of prasugrel, a novel P2Y ₁₂ receptor inhibitor in Tetrahedron Letters 53 (2012) 5364-5366, doi : 10.1016 / j. tetlet.2012.07.071 .
2. ↑ Ou, Wenhua; Yi, Weiyin; Liu, Feng; Pan, Xianhua; Peng, Xijiang: An improvement to the preparation of prasugrel hydrochloride in J. Chem. Res. 37 (2013) 369-371, doi : 10.3184 / 174751913X13687269227225 .
3. ↑ patent WO2009 / 98142 A1 (HELM AG 2009).
4. ↑ Takács-Novák, K .; Urac, M .; Horváth, P .; Völgyi, G .; Anderson, BD; Avdeef, A .: Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi's Facilitated Dissolution Method. A validation study in Eur. J. Pharm. Sci. 106 (2017) 133-144, doi : 10.1016 / j.ejps.2017.05.064 .
5. ↑ There is not yet a harmonized classification for this substance . A label of (R, S) -5- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -4,5,6,7-tetrahydrothieno [3.2] is shown, which is derived from a self-classification by distributors -c] pyridin-2-yl acetate in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 6, 2020.
6. ↑ New drugs: Efient® (Prasugrel). Drug information from the Drug Commission of the German Medical Association (AkdÄ), pp. 30–44. (As of April 16, 2009; 2.75MB, accessed March 19, 2010).
7. ↑ Gilles Montalescot et al: Pretreatment with Prasugrel in Non-ST-Segment Elevation Acute Coronary Syndromes. In: N Engl J Med. 369, 2013 September 12, pp. 999-1010, doi: 10.1056 / NEJMoa1308075 .
8. ↑ SD Wiviott et al .; TRITON-TIMI 38 Investigators: Prasugrel versus clopidogrel in patients with acute coronary syndromes. In: N Engl J Med. 357 (20), 2007 Nov 15, pp. 2001-2015. PMID 17982182 .
9. ↑ Final report A09-02: Prasugrel in acute coronary syndrome. (PDF) Institute for Quality and Efficiency in Health Care, July 11, 2011, accessed on July 6, 2020 . 
10. ↑ IQWiG: Prasugrel: For some patients, indications of added benefit, but also of greater harm. September 5, 2011, accessed August 9, 2013 . 
11. ↑ Wiebke Gogarten, Hugo Van Aken: Perioperative thrombosis prophylaxis - platelet aggregation inhibitors - importance for anesthesia. In: AINS - Anesthesiology · Intensive Care Medicine · Emergency Medicine · Pain Therapy. 47, 2012, pp. 242-252, doi: 10.1055 / s-0032-1310414 .

literature

• New drugs: Efient® (Prasugrel). Information from the Drugs Commission of the German Medical Association (AkdÄ). As of April 16, 2009 (PDF, 113 kB, accessed on March 19, 2010)
• F. Marzot, V. Pengo: Prasugrel for the treatment of patients with acute coronary syndrome. In: Vasc Health Risk Manag. 5 (1), 2009, pp. 321-324. Review. PMID 19436677 , PMC 2672466 (free full text)

Web links

• European Medicines Agency: EUROPEAN PUBLIC ASSESSMENT REPORT (EPAR) EFIENT EPAR summary for the public (pdf; 44 kB)
• Prasugrel evaluation in drug regulation in practice, Volume 36 · Edition 4 · July 2009, p. 90/91 408 kB, 24 p., Accessed on March 19, 2010

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !