Ifetroban Sodium: An Effective TxA₂/PGH₂ Receptor Antagonist

Abstract

This review presents a comprehensive discussion on the chemistry, pharmacokinetics, and pharmacodynamics of ifetroban sodium, a new thomboxane A 2 /prostaglandin H 2 receptor antagonist. Thromboxane A 2 is an arachidonic acid product, formed by the enzyme cyclooxygenase. In contrast to other cyclooxygenase products, thromboxane A 2 has been shown to be involved in vascular contraction and has been implicated in platelet activation. In general, results of clinical studies and animal experiments indicate that hypertension is associated with hyperaggregability of platelets and increased thomboxane A 2 levels in blood, urine, and tissues. The precursors to thromboxane A 2 , prostaglandin G 2 , and prostaglandin H 2 , also bind and activate the same receptors. Thus, a receptor antagonist was thought to be an improved strategy for reversing the actions of thromboxane A 2 /prostaglandin H 2 , rather than a thromboxane synthesis inhibitor. This review describes new methods for the synthesis and analysis of ifetroban, its tissue distribution, and its actions in a variety of animal models and disease states. We describe studies on the mechanisms of how ifetroban relaxes experimentally contracted isolated vascular tissue, and on the effects of ifetroban on myocardial ischemia, hypertension, stroke, thrombosis, and its effects on platelets. These experiments were conducted on several animal models, including dog, ferret, and rat, as well as on humans. Clinical studies are also described. These investigations show that ifetroban sodium is effective at reversing the effects of thromboxane A 2 -and prostaglandin H 2 -mediated processes.

Prostaglandins and Thromboxane Status in Patients with Cardiovascular Diseases in Ekiti State, Nigeria

“…According to the results obtained from this study, plasma levels of TXA2 was found to be significantly higher in stroke patients (p<0.05) which is similar to the work of [18]. Stroke has been found to be associated with hyperaggregability of platelets and increased thromboxane A2 levels in blood, urine, and tissues.…”

“…World health organisation in collaboration with the world heart federation and the world stroke organisation. 2011;3- 18…”

Thromboxane Inhibitors Attenuate Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administrations

“…The drug was administered daily as a bolus via intragastic tube at a dose of 3 mg/kg. At the dose administered, intestinal absorption of the drug is over 85% and it retains antagonism of thromboxane A2/prostaglandin endoperoxide (TP)‐receptor‐dependent responses for at least 24 hours after oral administration (Ogletree et al., ; Rosenfeld et al., ). Ifetroban is devoid of any agonistic activity.…”

Oxidized Products of α-Linolenic Acid Negatively Regulate Cellular Survival and Motility of Breast Cancer Cells

“…Furthermore, PP2 was also capable of inhibiting cellular migration in a Transwell assay (Figure 7A). Previous studies have suggested that thromboxane A2 receptor (TBXA2R) is involved in the migration and invasion of breast cancer cells [27,28] and that isoprostanes may also regulate the activation of TBXA2R [13].To determine if this signaling pathway was affected by PF1, a Transwell migration study was performed with a specific inhibitor (ifetroban) of TBXA2R [29]. We show that inhibition of this pathway by ifetroban was associated with reduced cellular migration (Figure 7B).…”