Disease relevance of Ifetroban

• Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group [1].
• In interaction studies, aspirin was injected i.v. 10 min prior to occlusion (10 mg/kg) and at the 45th min of ischemia (5 mg/kg) both with and without subsequent administration of ifetroban (0.3 mg/kg + 0.3 mg/kg per h) beginning at the 75th min of occlusion [2].
• BACKGROUND: To determine the results of standardized ulcer treatment regimes and effects of the oral thromboxane A2 antagonist Ifetroban (250 mg daily) on healing of chronic lower-extremity venous stasis ulcers [3].
• Dose-related cardioprotection by ifetroban in relation to inhibition of thrombosis and ex vivo platelet function [4].
• These observations suggest that a mechanism involving nitric oxide and potassium channels facilitates the reduction in basal tone produced by ifetroban in aortic rings of rats with aortic coarctation-induced hypertension [5].

High impact information on Ifetroban

• OBJECTIVES: The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2 receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure [1].
• Ifetroban improved the impaired endothelium-dependent relaxation in mesenteric vessels, but not in aortas and kidneys [6].
• In contrast, all inhibitors reduced clearance, i.e. uptake and degradation, of PGD(2) by hepatocytes: within 5 min uptake of 1 nmol/L PGD(2) was reduced from 43+/-5 fmol (controls) to 22+/-6 fmol (daltroban), 24+/-6 fmol (ifetroban) and 21+/-6 fmol (furegrelate) [7].
• 4. When the TxA2 receptor antagonists, Bay u 3405 (1 microM) and ifetroban (1 microM) were added to the superfusing medium, NPY did not alter either the frequency- or the concentration-response curves for either TNS or NA [8].
• To this end, we contrasted the effects of indomethacin, an inhibitor of cyclooxygenase, and of ifetroban, an antagonist of thromboxane A2/prostaglandin endoperoxide H2 receptors, on basal tone in aortic rings taken from normotensive and hypertensive rats [9].

Biological context of Ifetroban

• Ricinoleic acid also produced vasoconstriction (EC50 = 0.24 +/- 0.04 microgram/ml) that was sensitive to inhibition by ifetroban but not by indomethacin [10].
• This study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of ifetroban after i.v. and oral administrations of [14C]ifetroban or [3H]ifetroban in rats (3 mg/kg), dogs (1 mg/kg), monkeys (1 mg/kg), and humans (50 mg) [11].
• Chronic administration of a higher dose ifetroban (40 mg/kg/day) starting at 7 weeks of age was also without effect on blood pressure and stroke in noninstrumented saline-drinking SHRSP [12].
• 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 [13].

Anatomical context of Ifetroban

• Rings with endothelium from normotensive rats were unaffected by indomethacin and ifetroban [9].
• Ifetroban alone significantly (P < 0.05) reduced infarct size compared to vehicle treatment (13 +/- 1% vs. 23 +/- 2% of left ventricle), and this was not prevented by combination with aspirin (12 +/- 2% vs. 22 +/- 3% of left ventricle) [2].
• In dogs, ifetroban (1 + 1 mg/kg/h, intravenously, i.v.) or vehicle administration was initiated 10 min before left circumflex coronary artery (LCX) occlusion [14].
• Thus, doses of ifetroban causing profound TP receptor blockade also salvaged jeopardized myocardium in dogs and ferrets without changing collateral BF or peripheral hemodynamics [14].
• Additional experiments in ferrets tested the antithrombotic potency of ifetroban as an inhibitor of thrombotic cyclic flow reduction (CFR) in the stenosed abdominal aorta (Folts model) [4].

Associations of Ifetroban with other chemical compounds

• The increase in perfusion pressure (PP) produced by Ang II was studied in the absence or presence of the TXA2 receptor antagonist, ifetroban, or the ETA/ETB receptor antagonist, PD145065 [15].
• In vitro incubation of aortic rings from SHR with ifetroban also normalized relaxations to acetylcholine but had no effect in aorta from WKY [16].
• At the end of 3 days of administration, blood pressure in early 2K, 1C rats given losartan was reduced to levels of control rats, but remained slightly elevated in other groups and in those receiving ifetroban [17].
• Maximal inhibition of Ang II-induced vasoconstriction produced by the 3 antagonists was comparable in untreated WKY, but that of ifetroban and PD145065 was lower (P < 0.05) than that of prazosin in untreated SHR [18].

Gene context of Ifetroban

• COX-2 inhibition further reduced the PFA-100 closure time and enhanced platelet deposition in the smaller pulmonary arteries, effects that were attenuated by ifetroban [19].
• Effect of ifetroban, a thromboxane A2 receptor antagonist, in stroke-prone spontaneously hypertensive rats [12].
• High-dose ifetroban treatment did not prevent neutrophil (PMNL) accumulation measured as tissue myeloperoxidase activity in infarcted tissue [4].

Analytical, diagnostic and therapeutic context of Ifetroban

• Ifetroban was extensively metabolized after oral administration [11].
• METHODS: In a prospective, randomized, double blind, placebo-controlled multicenter study, 165 patients were randomized to Ifetroban (n = 83) versus placebo (n = 82) for a period of 12 weeks [3].
• Delaying initiation of treatment with high-dose ifetroban until 5 min into reperfusion also significantly reduced infarct size by 45% [4].

References