Disease relevance of sulfinpyrazone

• More on sulfinpyrazone after myocardial infarction [1].
• Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial [2].
• DATA SOURCES: English-language articles published after 1977 and indexed in MEDLINE under the following Medical Subject Heading terms: anticoagulants, aspirin, dipyridamole, ticlopidine, or sulfinpyrazone, combined with cerebrovascular disorders [3].
• Warfarin's anticoagulant effect was potentiated by 6 antibiotics (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, and miconazole); 5 cardiac drugs (amiodarone, clofibrate, propafenone, propranolol, and sulfinpyrazone); phenylbutazone; piroxicam; alcohol (only with concomitant liver disease); cimetidine; and omeprazole [4].
• The role of sulfinpyrazone in the prevention of arterio-venous shunt thrombosis [5].

High impact information on sulfinpyrazone

• Probenecid and sulfinpyrazone may therefore be useful lead compounds for the development of clinical reversal agents specific for MRP-mediated drug resistance [6].
• The two pyrazolon derivatives, phenylbutazone and sulfinpyrazone, selectively inhibit chemotactic peptide-induced effects on neutrophils [7].
• Sex difference in antithrombotic effect of sulphinpyrazone [8].
• The effects of sulphinpyrazone on heart-rate and blood-pressure responses to exercise were assessed in 15 normal volunteers by a randomised double-blind crossover technique [9].
• Chest tube drainage measured within the first 35 hr after CABG revealed that the median loss with aspirin daily (965 ml), aspirin three times daily (1175 ml), and aspirin plus dipyridamole (1000 ml) exceeded (p less than .02) that with placebo (805 ml), while median loss with sulfinpyrazone (775 ml) did not [10].

Chemical compound and disease context of sulfinpyrazone

• Thus, sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin stereoselectively by reduced metabolic clearance of S-warfarin [11].
• The Randomized Trial of Aspirin and Sulfinpyrazone in Threatened Stroke compared aspirin (325 mg four times daily), sulfinpyrazone (200 mg four times daily) and aspirin plus sulfinpyrazone with placebo in patients with transient cerebral ischemia [12].
• In cerebrovascular disease there is reasonable evidence that the administration of sulfinpyrazone can significantly reduce cerebral ischemia or mortality, but similar trials performed with aspirin, dipyridamole or clofibrate failed to reveal a significant difference in favor of the experimental treatment [13].
• Prevention of postoperative deep vein thrombosis by a combination of subcutaneous heparin with subcutaneous dihydroergotamine or oral sulphinpyrazone [14].
• It is concluded that patients with abnormal cardiac valves and raised plasma levels of beta tg or PF4 have, despite warfarin, a consumption coagulopathy that can be inhibited by sulphinpyrazone [15].

Biological context of sulfinpyrazone

• These results are consistent with reports of the effects of sulfinpyrazine on platelet involvement in other conditions, and suggest that the drug reduces platelet activation and inhibits actual destruction [16].
• The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated [17].
• Both aspirin and sulfinpyrazone eliminated the rise in thromboxane B2 and the increase in pulmonary vascular resistance seen in control animals [18].
• Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfinpyrazone had been administered previously [19].
• ATP-dependent [3H]GSH transport was cis-inhibited by substrates of the yeast Ycf1p transporter and inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, probenecid, and sulfinpyrazone, inhibitors of MRP1 and MRP2, but was minimally affected by membrane potential or pH gradient uncouplers [20].

Anatomical context of sulfinpyrazone

• Platelet function in coronary artery disease: effects of coronary surgery and sulfinpyrazone [16].
• Sulfinpyrazone reduces the thrombotic occlusion of arteriovenous cannulae and early occlusion of saphenous vein aortocoronary grafts [21].
• Sulfinpyrazone lengthened platelet survival in 12 of 24 (50%) treated patients but this drug did not alter either arterial oxygen tension arterial carbon dioxide tension, or pulmonary artery pressure [22].
• These data suggest that sulfinpyrazone may protect endothelial cells from injury in vivo by some apparently indirect mechanism [23].
• A patient with recurrent thrompophlebitis had sterile pyuria with white blood cell casts and transient, mild renal failure during therapy with sulfinpyrazone [24].

Associations of sulfinpyrazone with other chemical compounds

• Nonsteroidal anti-inflammatory drugs and sulfinpyrazone compete dose-dependently with arachidonate for binding to platelet cyclooxygenase [25].
• Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease [26].
• Moreover, using inhibitors of GST (dicumarol) or MRP1 (sulfinpyrazone), it was shown that in MCF7 cells resistance to chlorambucil requires both intact MRP1-dependent efflux pump activity and, for full protection, GST A1-1 catalytic activity [27].
• In line with this, transport of the lipid to the exoplasmic leaflet depended on the intracellular glutathione concentration and was inhibited by the MRP1-inhibitors sulfinpyrazone and indomethacin, but not by the MDR1 P-glycoprotein inhibitor PSC 833 [28].
• The inhibitory effects of sulfinpyrazone are more marked ex vivo than in vitro, suggesting biotransformation to potentially active metabolites such as the sulfide and sulfone metabolites [29].

Gene context of sulfinpyrazone

• Finally, we found that sulfinpyrazone stimulated [3H]E217betaG transport by wild-type MRP2 4-fold, whereas transport by the Trp1254 substituted mutants was enhanced 6-10-fold [30].
• Inhibitors of glutathione synthesis (BSO), GSTs (curcumin, ethacrynic acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect of GSTP1 AS RNA [31].
• We demonstrate that glutathione transport in MDCKII-MRP1 cells is inhibited by the inhibitors of organic anion transporters sulfinpyrazone, indomethacin, probenecid and benzbromarone [32].
• Sulfinpyrazone only stimulated MRP2, but inhibited MRP4 [33].
• Treatment with sulphinpyrazone resulted in lengthening of both platelet and fibrinogen survival, a rise in ATIII but no change in the beta tg or PF4 concentrations [15].

Analytical, diagnostic and therapeutic context of sulfinpyrazone

• In postoperative hip arthroplasty patients, treatment with aspirin and sulfinpyrazone resulted in a statistically significant reduction of venographically diagnosed thrombi in the proximal veins of the leg [34].
• Submaximal exercise tests were performed 1 and 2 hours after either sulphinpyrazone (SPZ) 200 mg orally or placebo [9].
• The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months [5].
• This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis [5].
• In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients [35].

References