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Ifetroban sodium: an effective TxA2/PGH2 receptor antagonist Rosenfeld L; Grover GJ; Stier CT JrCardiovasc Drug Rev 2001[Sum]; 19 (2): 97-115This review presents a comprehensive discussion on the chemistry, pharmacokinetics, and pharmacodynamics of ifetroban sodium, a new thomboxane A2/prostaglandin H2 receptor antagonist. Thromboxane A2 is an arachidonic acid product, formed by the enzyme cyclooxygenase. In contrast to other cyclooxygenase products, thromboxane A2 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 A2 levels in blood, urine, and tissues. The precursors to thromboxane A2, prostaglandin G2, and prostaglandin H2, also bind and activate the same receptors. Thus, a receptor antagonist was thought to be an improved strategy for reversing the actions of thromboxane A2/prostaglandin H2, 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 A2- and prostaglandin H2-mediated processes.|Animals[MESH]|Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics/*pharmacology/therapeutic use[MESH]|Humans[MESH]|Hypertension/prevention & control[MESH]|Muscle Contraction/drug effects[MESH]|Muscle, Smooth, Vascular/drug effects[MESH]|Myocardial Ischemia/prevention & control[MESH]|Oxazoles/pharmacokinetics/*pharmacology/therapeutic use[MESH]|Platelet Aggregation Inhibitors/pharmacokinetics/*pharmacology/therapeutic use[MESH]|Prostaglandin H2[MESH]|Prostaglandins H/*metabolism[MESH]|Randomized Controlled Trials as Topic[MESH]|Receptors, Prostaglandin/*antagonists & inhibitors[MESH]|Receptors, Thromboxane/*antagonists & inhibitors[MESH]|Stroke/prevention & control[MESH]|Thrombosis/prevention & control[MESH]|Thromboxane A2/*metabolism[MESH] |
