Laropiprant

[(3R)-4-(4-Chlor-benzyl)-7-fluor-5-methansulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-essigsäure

C10AD52, nicotinic acid combination drug

Vasoconstriction

Prostaglandin D2 receptor antagonist

Template: Infobox chemical / molecular formula search available

Laropiprant is a drug from the group of prostaglandin antagonists. In combination with the lipid-lowering nicotinic acid used for the treatment of dyslipidemia he should reduce nicotinsäurebedingte side effects of the flush syndrome (flushing ). The MAH presented the distribution of in about 70 countries ( in Europe under the brand name Tredaptive ) approved nicotinic acid laropiprant combination a world after the end of 2012 data from the cardiovascular endpoint study HPS2 - THRIVE were known with Tredaptive. In a Red Hand Letter from the manufacturer Merck & Co., Inc. pointed out that the treatment must be terminated with laropiprant.

Pharmacology

Mechanism of Action

Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1 ). DP1 by prostaglandin D2 ( PGD2 ) is activated; this leads to increased cAMP secretion, resulting in dilatation of the skin vessels result. The patient suffers from a strong feeling of warmth with skin redness and itching, a flush syndrome. Nicotinic acid ( other names: niacin, vitamin B3) is stimulated PGD2 synthesis.

Pharmacokinetic properties

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

Risk-benefit ratio

In December 2012, it was announced that in cardiovascular outcomes trial HPS2 - THRIVE ( Heart Protection Study 2 - Treatment of HDL to Reduce the Incidence of Vascular Events ), the primary endpoint " reduction of serious vascular events " was not achieved. Also in combination with a statin reduced Tredaptive not the risk of serious vascular events. With this combination, however, the incidence of some serious non-fatal adverse events compared with statin monotherapy was statistically significantly increased, which is why Merck & Co., Inc. sales Tredaptive ceased worldwide and an expected ban forestalled.