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At least 19 recordsLinked to original sources

PubMed1977

Effects of sulfinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin.

Sulfinpyrazone added to PRP inhibited the release of serotonin induced by collagen. The inhibitory effect depended strongly on the strength of the collagen stimulus. Serotonin release was also inhibited (up to 73%) in PRP prepared from subjects who had ingested the drug. This is the first demonstration of a direct effect of a sulfinpyrazone in vivo on in vitro tests of platelet function. Prostaglandin synthesis was studied with lysates of washed platelets, arachidonic acid-14C, and silicic acid chromatography to isolate a reaction product which was tentatively identified as thromboxane B2. Platelet prostaglandin synthesis was shown to be strongly inhibited by sulfinpyrazone. Inhibition was competitive with respect to substrate. It is proposed that effects of sulfinpyrazone on platelet function may be due to inhibition of prostaglandin synthesis. The competitive nature of sulfinpyrazone inhibition may explain why sulfinpyrazone is a strong inhibitor of the release reaction under conditions of dilute collagent stimulation but is weak in the presence of stronger stimuli. In comparing the potency of inhibitors of platelet prostaglandin synthesis the nature of inhibition must be considered. Competitive inhibitors may be incorrectly regarded as weak if studied only at high substrate concentration.

Blood Platelets↗

PubMed1975

Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan) in man.

The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2'-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a 14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 mug/ml, respectively, after 1 - 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total 14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites. i.e. the sulphone G 31 442, the "para-hydroxy"=compound G 32 642 and the "4-hydroxy"- compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as "para-hydroxy"-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as "4-hydroxy"-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-beta-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.

Adult↗

PubMed1979

The effect of sulfinpyrazone on morphological changes in the coronary vasculature induced by prolonged unpredictable stress in the rat.

It was confirmed that prolonged unpredictable stress in the rat induces morphological change in the coronary microcirculation. These changes include dilation in venules, deposits staining positive with PAS in the venules due to platelet aggregation and a breakdown of the endothelial lining in arterioles. Sulfinpyrazone is reported to prevent platelet agglutination, and shows effectiveness in the clinic in preventing re-infarction following infarction. Accordingly rats were exposed to the stress regimen for 50 days, and groups were treated with sulfinpyrazone, either prophylactically (receive drug for 50 days) or therapeutically (receive drug Day 30 to Day 50). The morphology of the hearts of treated animals were compared with those of placebo treated controls. It was demonstrated that therapeutic sulfinpyrazone did not prevent (p less than 0.01), but reduced the incidence of morphological change in the coronary microcirculation. Prophylactic sulfinpyrazone had a distinct protective effect (p less than 0.001). It was demonstrated that the plasma corticosterone levels in both drug groups did not fall to the level found in control groups. The results are discussed in terms of a glucocorticoid-sulfinpyrazone interaction preventing prostaglandin release which will prevent platelet aggregation. It is possible that the interaction relates to maintaining the integrity of the microcirculatory endothelial cells, thus preventing the local release of inflammatory substances.

Animals↗

PubMed1977

Sulfinpyrazone and postoperative deep vein thrombosis.

Small doses of subcutaneous heparin and infusions of dextran both reduce the incidence of fatal pulmonary embolism after elective general surgery. But both methods have disadvantages. Therefore, the protection against deep vein thrombosis afforded by sulfinpyrazone, a drug which can be taken by mouth as well as by injection, was assessed in a prospective study of 119 patients undergoing elective general or urological surgery. The prophylactic administration of sulfinpyrazone was compared with the effects of small doses of sodium heparin and infusions of dextran-70. The 125I-fibrinogen test was carried out in all patients during their hospitalization. Deep vein thrombosis was diagnosed in 13 of 30 patients (43%) who received sulfinpyrazone, in 9 of 29 (31%) receiving dextran-70 and in 2 of 22 (9%) having subcutaneous heparin. The difference between the sulfinpyrazone and heparin groups was statistically significant (p less than 0.01). Sulfinpyrazone in the dose used in this trial was not effective in reducing the incidence of deep vein thrombosis during elective general surgery.

Administration, Oral↗

PubMed1978

Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Trial.

The Anturane Reinfarction Trial is a randomized, double-blind, multicenter clinical trial comparing sulfinpyrazone (200 mg four times a day) and placebo in the prevention of cardiac mortality among patients with a recent documented myocardial infarction. Results represent data accumulated on 1475 cligible patients entered 25 to 35 days after myocardial infarction and followed for an average of 8.4 months. The data reflect excellent randomization, compliance with therapy and tolerance of the drug. All 69 deaths were a cardiovascular nature (68 cardiac and one cerebrovascular). For cardiac deaths, the annual death rate was 9.5 per cent in the placebo group and 4.9 per cent in the sulfinpyrazone group, representing an observed reduction of 48.5 per cent (P = 0.018). The annual sudden-cardiac-death rate was 6.3 per cent for the placebo and 2.7 per cent for the sulfinpyrazone group, representing a 57.2 per cent reduction in sudden-cardiac-death rate (P = 0.015). Sulfinpyrazone appears to be effective in reducing cardiac deaths during the first year after myocardial infarction.

Aged↗

PubMed1975

Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease.

Platelet survival time was measured (autologous labelling with 51chromium) in 68 men with coronary artery disease (CAD). Survival was shortened slightly (3.2 +/- 0.04 days; mean +/- SEM) as compared to normal (3.7 +/- 0.04 days; N = 18; P less than 0.001), and 60% had shortened survival (less than 3.3 days). Thirty-seven had hyperlipoproteinemia (36 with Type IV and one with Type III) and platelet survival was shortened (3.1 +/- 0.10 days) and significantly different from survival of men with normal lipoproteins (3.3 +/- 0,12 days; P less than 0.05). Twenty-two with shortened platelet survival and CAD received either clofibrate or sulfinpyrazone. Clofibrate prolonged platelet survival (2.6 +/- 0.09 to 3.4 +/- 0,14 days; P less than 0.001) and ten of 12 had prolongation of survival. Sulfinpyrazone increased survival (2.8 +/- 0.12 to 3.6 +/- 0.21; P less than 0.001) and nine of ten had prolognation of platelet survival. Clofibrate lowered serum cholesterol and tryglyceride but alteration in lipids did not correlate with alteration of survival. Sulfinpyrazone did not alter lipids. Data suggest that survival is shortened in CAD and that clofibrate and sulfinpyrazone alter survival. Platelet suppressant agents may prove beneficial in reducing the extent and complications of atherosclerotic arterial injury.

Adult↗

PubMedDate not supplied

Effect of sulfinpyrazone on platelet survival time in patients with transient cerebral ischemic attacks.

Platelet suppressant drugs have been suggested as beneficial for patients with transient cerebral ischemic attacks and these drugs have been shown to lengthen shortened platelet survival time. In the present study platelet survival time (autologous labeling with 51Chromium) was measured in 25 patients with transient cerebral ischemia involving a carotid distribution. Platelet survival was shortened in all patients (2.5 +/- 0.10 days; AVE t 1/2 +/- SEM; Normal 3.7 +/- 0.04 days P less than 0.001). Sulfinpyrazone increased platelet survival in 9 of 19 (47%) of patients (2.4 +/- 0.10 to 2.8 +/- 0.16 days; P less than 0.01). Of the 19 treated with sulfinpyrazone, 10 had a marked reduction in the frequency of transient ischemic episodes and an increased in platelet survival (2.6 +/- 0.16 to 3.1 +/- 0.22 days; P less than 0.01) was observed in all patients. Three patients had no benefit from sulfinpyrazone and alteration of platelet survival did not occur. Results suggest that platelet survival is shortened in patients with transient cerebral ischemia, that sulfinpyrazone increases platelet curvival and may decrease the frequency of ischemic episodes, and that there may be a relationship between clinical benefit and alteration of platelet survival time.

Adult↗

PubMed1979

Determination of sulfinpyrazone and two of its metabolites in human plasma and urine by gas chromatography and selective detection.

A selective and sensitive gas chromatographic method for simultaneous determination of sulfinpyrazone and two of its metabolites (the para-hydroxylated metabolite and the sulfone metabolite) in biological fluids using alkali flame ionization detection (AFID), electron capture detection (ECD) and mass fragmentographic detection is described. The compounds are extracted from the samples, methylated and separated on 2% OV-17 or 3% OV-225 columns. Phenylbutazone is used as internal standard. Standard curves are linear. The coefficient of variation at 10 microgram/ml of sulfinpyrazone in plasma was shown to be 1.8% (AFID), and the detection limits were 0.1 microgram/ml (AFID) and 10 ng/ml (ECD). Mass spectra of the methylated compounds are shown and serum concentration curves after oral administration of 100 mg sulfinpyrazone to two persons are determined together with the excreted amounts of drug and metabolites.

Flame Ionization↗

PubMed1978

[Effect of sulfinpyrazone on enhanced platelet aggregation in vitro (author's transl)].

Adding sulfinpyrazone in a concentration of 500 and 250 microgram/ml to blood of patients with enhanced platelet stickiness a significant decrease (p less than 0.01) of the maximum amplitude and the aggregation velocity could be demonstrated with the spontaneous platelet aggregation test, PAT III, of Breddin, as well as with the collagen and the ristocetin induced aggregation. The lower concentration of 50 microgram/ml of sulfinpyrazone yielded the same results when aggregation was induced with the higher concentrations of 1.5 microgram/ml ristocetin and 5 microgram/ml collagen. Only the maximum aggregation velocity of the PAT III was significantly reduced after addition of 50 microgram sulfinpyrazone/ml blood. With sufficient concentrations of sulfinpyrazone the anti-aggregating action of this substance can very well be demonstrated with the aggregation induced by ristocetin or collagen and the PAT III. The effect is dose dependent.

Aged↗

PubMed1978

[Inhibition of cancer cell stickiness, a model for the testing of in vivo thrombocyte aggregation inhibitors. IV. Effect of sulfinpyrazone].

It has been shown that sulfinpyrazone is able to interfere with the dynamic interaction between sticky Walker-256-carcinosarcoma cells and the vascular endothelium. This effect is due to a dose-dependent inhibition of platelet adhesiveness and aggregation to sticky circulating tumor cells and their consequent attachment to the vascular endothelium as observed by means of intravital capillary microscopy in the mesentery of rats. Further proof of these investigations was that sulfinpyrazone led to a dose-dependent inhibition of the immediate drop of circulating platelets and reduced significantly the lethal pulmonary tumor cell embolism which occurred in 57.5% of the controls within 5-10 minutes after intravenous transplantation of 1 X 10(6) Walker-256-carcinosarcoma cells. These results are interpreted in an inhibition of platelet adhesiveness and aggregation in vivo by sulfinpyrazone.

Animals↗

PubMed1976

Abnormalities of urinary sediment and renal failure following sulfinpyrazone therapy.

A patient with recurrent thrompophlebitis had sterile pyuria with white blood cell casts and transient, mild renal failure during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during a second course of sulfinpyrazone therapy.

Acute Kidney Injury↗

PubMed1979

Sulfinpyrazone kinetics after intravenous and oral administration.

Sulfinpyrazone kinetics has been investigated after intravenous and oral doses. They may be described by a 3-compartment open model. In the body about half the drug is in the plasma or in interstitial fluids, which equilibrated with plasma. Most of the rest is in an extravascular compartment, from which it easily diffuses back to the plasma. About 3% of the dose is still in the body after 24 hr and is located mainly in a deep compartment. After oral administration, sulfinpyrazone is quickly absorbed, largely from the stomach.

Administration, Oral↗

PubMed1979

Interference by sulfinpyrazone and salicylate of aspirin inhibition of platelet cyclooxygenase activity.

The irreversible effect of acetylsalicylic acid on platelet cyclooxygenase activity is inhibited by salicylate and by sulfinpyrazone. Since acetylsalicylate is rapidly hydrolysed in plasma to salicylate which has a relatively prolonged half life in plasma, it is possible that persistant elevation of plasma salicylate may interfere with the efficacy of subsequent doses of aspirin. Sulfinpyrazone is sometimes used in combination with aspirin, and could interfere with the efficacy of aspirin on platelets. This theoretical possibility would be more likely to occur at lower doses of aspirin.

Aspirin↗

PubMed1978

A randomized trial of aspirin and sulfinpyrazone in threatened stroke.

Five hundred and eighty-five patients with threatened stroke were followed in a randomized clinical trial for an average of 26 months to determine whether aspirin or sulfinpyrazone, singly or in combination, influence the subsequent occurrence of continuing transient ischemic attacks, stroke or death. Eighty-five subjects went on to stroke, and 42 died. Aspirin reduced the risk of continuing ischemic attacks, stroke or death by 19 per cent (P less than 0.05) and also reduced risk for the "harder," more important events of stroke or death by 31 percent (P less than 0.05), but this effect was sex-dependent: among men, the risk reduction for stroke or death was 48 per cent (P less than 0.005), whereas no significant trend was observed among women. For sulfinpyrazone, no risk reduction of ischemic attacks was observed, and the 10 per cent risk reduction of stroke or death was not statistically significant. No overall synergism or antagonism was observed between the two drugs. We conclude that aspirin is an efficacious drug for men with threatened stroke.

Aspirin↗

PubMed1976

Antithrombotic effects of sulfinpyrazone in animals: influence on fibrinolysis and sodium arachidonate-induced pulmonary embolism.

It has been shown that sulfinpyrazone stimulates fibrinolytic activity in various in vitro and in vivo test systems. In rats with kaolin-induced paw oedema this compound is able to restore the markedly prolonged euglobulin clot lysis time in an oral dose of 30 mg/kg, whereas salicylate and dipyridamole are somewhat less active in this respect. Beside these effects, sulfinpyrazone protects rabbits from arachidonate-induced sudden death after a single oral dose of 10-30 mg/kg.

Animals↗

PubMed1979

A controlled study of the effect of sulfinpyrazone on platelet survival and on platelet-bound 14C-serotonin release in patients with previous myocardial infarction.

Preliminary data obtained in the ambit of Anturan Reinfarction Italian Study (ARIS) show that, in postmyocardial infarction, reduced platelet survival time occurred in hyperbetalipoproteinemic patients treated with placebo, but not in the group of patients treated with sulfinpyrazone (interaction between treatment and lipemic level is at p approximately equal to 0.1). The sulfinpyrazone effect on platelet survival is probably related to the release reaction inhibition as suggested by our ex vivo results on platelet-bound 14C-serotonin release.

Adult↗

PubMed1978

Comparison of antithrombotic activity of heparin, ASA, sulfinpyrazone and VK 744 in a rat model of arterial thrombosis.

Rat carotid arteries were injured electrically (350 V, 2 mA DC for 5 min) before and after the intravenous administration of heparin (1,000 U/kg), VK 744 (25, 50, 100 mg/kg) ASA (100, 200 mg/kg) and sulfinpyrazone (50, 100, 150, 200 mg/kg). Thrombus growth was quantified by recording arterial temperature change distal to the injury. Heparin completely blocked thrombus formation in most experiments. All other agents exhibited antithrombotic activity with sulfinpyrazone being most potent. None was as effective as heparin. This model may be a useful tool for screening antithrombotic drugs.

Animals↗

PubMed1979

Effects of acetylsalicylic acid, sulfinpyrazone and dipyridamole on platelet adhesion and aggregation in flowing native and anticoagulated blood.

The interaction of rabbit platelets with subendothelium of rabbit aorta was investigated under controlled blood flow conditions. Platelet adhesion and thrombus formation were compared after perfusion of native blood and of blood anticoagulated with citrate, heparin or heparin plus citrate. 15 mM citrate in plasma caused significant reduction of aggregation, thrombus volume and thrombus height; adhesion was concomitantly increased. Heparin (500 U/kg) had no significant effect on adhesion and thrombus dimensions. Treatment of rabbits with acetylsalicylic acid or sulfinpyrazone caused a significant reduction of thrombus volume and thrombus height in the presence of citrate. However, no significant effects were observed in native or heparinized blood. It is concluded that low citrate concentrations: (1) inhibit thrombus growth; (2) enhance thrombus breakdown; (3) therefore increase adhesion, and (4) strongly enhance a possible inhibitory effect of acetylsalicylic acid and sulfinpyrazone on thrombus growth.

Animals↗