Disease relevance of SULOTROBAN

• Myocardial infarction was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group, 1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030) [1].
• Pharmacokinetics of the thromboxane A2 receptor antagonist sulotroban (BM 13.177) in renal failure [2].
• Thrombus formation in rats induced by vascular damage is strongly reduced by combining doses of iloprost and sulotroban (BM 13.177) which given alone are ineffective [3].
• The inhibition of collagen-induced aggregation and thrombocytopenia by sulotroban was negligible on Dahl-R rats but significant in Dahl-S rats [4].
• TX receptor antagonizing substances such as BM 13177 and specific PAF antagonists for example BN 52021 and WEB 2086, completely inhibited the PAF induced cardiac arrhythmias [5].

High impact information on SULOTROBAN

• The goal of this study was to assess the effects of aspirin (a nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective blocker of the thromboxane A2 receptor) on late clinical events and restenosis after PTCA [1].
• While both aspirin and sulotroban prevent the occurrence of myocardial infarction, overall clinical outcome appears superior for aspirin compared with sulotroban [1].
• Bradykinin mobilized 9.4% of intracellular calcium stores in cardiomyocytes as assessed by chlortetracycline-based fluorometry, and this effect of bradykinin was blocked by BM 13177 or the B2 bradykinin receptor blocker Hoe 140 by more than 70% [6].
• In two-week-old diabetic rats, a specific TXA2 synthetase inhibitor, OKY-046, or a specific TXA2 receptor antagonist, Sulotroban, increased renal vascular resistance (RVR) and ameliorated the hyperperfusion [7].
• In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo [8].

Chemical compound and disease context of SULOTROBAN

• Effect of selective endoperoxide/thromboxane A2 receptor antagonism with sulotroban on tPA-induced thrombolysis in a rabbit model of femoral arterial thrombosis [9].

Biological context of SULOTROBAN

• Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists [8].
• The log (1/IC50) values for 6 (n = 8), which forms a 12-membered ring similar to the one observed for S-145, were found to be maximal values in 1-8 and were comparable to those for BM-13177 [10].
• The renal clearance of sulotroban exceeded the glomerular filtration rate, suggesting renal secretion of sulotroban [11].
• Diuresis, characterized by increases in both fractional and absolute urinary excretion of sodium, potassium, chloride and calcium, and decreases in urine osmolality occurred at each of the sulotroban dosages tested [11].
• In this study, we have demonstrated for the first time by using U 46619, a stable analogue of thromboxane A2 (TXA2), that TXA2 exerts a cell proliferative effect on HeLa cells which is mediated by specific TXA2 receptors, inasmuch as the cell proliferation could be dose-dependently suppressed by TXA2 receptor antagonist BM 13177 [12].

Anatomical context of SULOTROBAN

• The thrombolytic efficacy of recombinant tissue-type plasminogen activator (tPA) in the presence and absence of the selective endoperoxide/thromboxane A2 (TXA2) receptor antagonist, sulotroban (BM 13.177, SK&F 95587) was studied in a model of femoral artery thrombosis in the anesthetized rabbit [9].
• Hirudin and sulotroban improve coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary artery thrombosis [13].

Associations of SULOTROBAN with other chemical compounds

• The stable PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban (BM 13177) were investigated for possible synergistic effects on platelet aggregation in human platelet rich plasma in vitro [14].
• Indeed, its affinity for human washed platelet TXA2 receptors labeled with [3H]SQ-29548 (IC50 = 0.0078 microM) is higher than sulotroban (IC50 = 0.93 microM) and SQ-29548 (IC50 = 0.021 microM) [15].
• The effects of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and of the TXA2 receptor antagonist BM 13177 on blood pressure and on the efficiency of antihypertensive drugs were investigated in spontaneously hypertensive rats (SHR) [16].

Gene context of SULOTROBAN

• During lysis there was an increase in plasma beta-thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone [8].
• Sulotroban was without effect on responses to endothelin (ET)-1, sarafotoxin (S) 6a or S6c and platelet-activating factor (PAF) [17].
• At low PAF concentrations aggregation and BTG release were blocked by apyrase (a scavenger of ADP), by ASA (an inhibitor of cyclooxygenase) and by BM 13177 (a thromboxane receptor antagonist) [18].

Analytical, diagnostic and therapeutic context of SULOTROBAN

• METHODS AND RESULTS: Patients (n = 752) were randomly assigned to aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6 hours before PTCA and continued for 6 months [1].
• Infusions of either vehicle or sulotroban were continued for 2 hr, post-thrombolysis. tPA was infused for at least 30 min, after which infusion of tPA was terminated upon achieving a reperfusion level of coronary blood flow equivalent to 50% or greater than control blood flow [19].
• The plasma and urine concentrations of sulotroban were measured by gas-chromatography over 72 h and the pharmacokinetic parameters were calculated [2].
• The significant increase in TXB2 concentrations in plasma and bronchoalveolar lavage (BAL) after ET-1 challenge (15-fold and 4-fold, respectively) have been reduced or abolished by ASA as well as HOE 944 and not altered by BM 13177 [20].
• Sulotroban during and after coronary angioplasty. A double-blind, placebo controlled study [21].

References