Laropiprant

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Structural formula
Structural formula laropiprant
General
Non-proprietary name Laropiprant
other names

[(3 R ) -4- (4-chloro-benzyl) -7-fluoro-5-methanesulfonyl-1,2,3,4-tetrahydrocyclopenta [b] indol-3-yl] acetic acid ( IUPAC )

Molecular formula C 21 H 19 ClFNO 4 S
External identifiers / databases
CAS number 571170-77-9
EC number 682-424-1
ECHA InfoCard 100.207.712
PubChem 9867642
ChemSpider 8043333
DrugBank DB11629
Wikidata Q412291
Drug information
ATC code

C10 AD52 , nicotinic acid combination drug

Drug class

Vasoconstriction

Mechanism of action

Prostaglandin D2 receptor - antagonist

properties
Molar mass 435.90 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Laropiprant is a drug from the group of prostaglandin antagonists. In combination with the lipid-lowering agent nicotinic acid used to treat fat metabolism disorders, it is said to reduce nicotinic acid- related side effects of flush syndrome ( blushing ). The marketing authorization holder discontinued the worldwide sale of the nicotinic acid / laropiprant combination approved in around 70 countries (in Europe under the brand name Tredaptive ) after data from the HPS2-THRIVE cardiovascular endpoint study with Tredaptive became known at the end of 2012 .

pharmacology

Mechanism of action

Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1). DP1 is activated by prostaglandin D2 (PGD2); this leads to an increased release of cAMP , which leads to a dilatation of the skin vessels. The patient suffers from a strong sensation of warmth with reddening of the skin and itching, a flush syndrome . The PGD2 synthesis is stimulated by nicotinic acid (other names: niacin, vitamin B 3 ).

Pharmacokinetic properties

Laropiprant has a plasma protein binding of greater than 99% and a plasma half-life of 12 to 17.7 hours.

Risk-benefit ratio

In December 2012, it became known that the primary endpoint “Reduction of serious vascular events” was not achieved in the cardiovascular endpoint study HPS2-THRIVE (Heart Protection Study 2 - Treatment of HDL to Reduce the Incidence of Vascular Events) . Even when combined with a statin, Tredaptive did not reduce the risk of serious vascular events. However, with this combination, the incidence of some serious non-fatal adverse side effects was statistically significantly higher than with statin monotherapy, so Merck & Co., Inc. stopped selling Tredaptive worldwide and anticipated an expected ban.

In a red-hand letter in 2013, Merck informed that treatment with laropiprant had to be stopped.

literature

  • E. Lai, LA Wenning, TM Crumley, I. De Lepeleire, F. Liu, JN de Hoon, A. Van Hecken, M. Depré, D. Hilliard, H. Greenberg, G. O'Neill, K. Metters, KG Gottesdiener, JA Wagner: Pharmacokinetics, pharmacodynamics, and safety of a prostaglandin D2 receptor antagonist. In: Clinical pharmacology and therapeutics Volume 83, Number 6, June 2008, pp. 840-847, doi : 10.1038 / sj.clpt.6100345 . PMID 17882161 .
  • JF Paolini, YB Mitchel, R. Reyes, U. Kher, E. Lai, DJ Watson, JM Norquist, AG Meehan, HE Bays, M. Davidson, CM Ballantyne: Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia . In: The American journal of cardiology Volume 101, Number 5, March 2008, pp. 625-630, doi : 10.1016 / j.amjcard.2007.10.023 . PMID 18308010 .

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ MSD stops selling Tredaptive® , DAZ-online January 14, 2013.
  3. ^ European Medicines Agency: European Medicines Agency starts review of Tredaptive, Pelzont and Trevaclyn
  4. ↑ Rote-Hand-Brief from MSD dated December 27, 2012 (PDF; 1.8 MB) Retrieved January 3, 2013 .
  5. ↑ Rote-Hand-Brief from MSD of January 21, 2013 (PDF; 1.6 MB) Retrieved January 23, 2013 .