Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases

Abstract

Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several pharmacological and clinical limitations that have prompted the search for more effective platelet antagonists. The candidates include various blockers of the purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine; two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor: ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be administered both intravenously and orally); BX 667, an orally active and reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH 602539 and E5555, highly selective and orally active antagonists on the protease-activated receptor 1. A number of drugs also hit new targets: terutroban, an oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a second-generation, nuclease resistant aptamer which inhibits von Willebrand factordependent platelet aggregation; ALX-0081, a bivalent humanized nanobody targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4 monoclonal antibody of von Willebrand factor. The pharmacology and clinical profiles of new platelet antagonists indicate that they provide more consistent, more rapid and more potent platelet inhibition than agents currently used. Whether these potential advantages will translate into clinical advantages will require additional comparisons in properly powered, randomized, controlled trials.

A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

“…Nanobodies have been applied in multiple fields of medicine as a novel antibody drug. [34][35][36] However, there have been no reports of any anti-rSPA nanobodies for lung-targeting ligands.…”

A gyógyszer indukálta vérzékeny betegek fogorvosi, szájsebészeti ellátása: a 2015-ös hazai szakmai ajánlás alkalmazása és értékelése

“…Az úgynevezett új típusú antikoaguláns gyógyszereket szedő páciensek fogászati beavatkozásainak vérzéses kockázatairól még viszonylag kevés tanulmány található az irodalomban. Általánosságban elmondható, hogy a leggyakoribb fogorvosi/szájsebészeti kezelések előtt nem szükséges a gyógyszerszedést módosítani [16][17][18][19][20][21][22][23].…”

How to manage prasugrel and ticagrelor in daily practice

“…Clopidogrel is a prodrug that requires metabolisation into an active metabolite by several hepatic cytochromes and through various mechanisms that can be altered in some patients. Recently, new antiplatelet drugs targeting the P2Y12 receptor, namely prasugrel and ticagrelor, have been introduced for the secondary prevention of thrombosis in patients with ACS [3][4][5]. These new drugs have been shown to inhibit the P2Y12 receptor more rapidly and more effectively than clopidogrel.…”