SEARCH · PubMed Health

Results for “SULFINPYRAZONE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1980

New metabolites of sulfinpyrazone in man.

The disposition and metabolism of sulfinpyrazone have been studied after oral administration of 100 mg 14C-labelled drug to two male volunteers. The results confirmed earlier observations on the kinetics and biotransformation of the drug in man. Additionally, four new metabolites were identified and quantified, i.e., the sulfide analogue G 25 671 of sulfinpyrazone (Anturano), the p-hydroxy-sulfide G 33 378, the p-hydroxy-sulfone CGP 17 385 and the C(4)-glucuronide of the sulfide. In plasma, the area under the concentration-time curve (0--24 h) of sulfinpyrazone was, on an average, 61.7% of that of total 14C-substances. The AUC-value for the sulfide and the sulfone corresponded to 13.4 and 6.0%, respectively. The other, specifically measured plasma metabolites (p-hydroxy-sulfin-pyrazone, p-hydroxy-sulfide, p-hydroxy-sulfone and 4-hydroxy-sulfinpyrazone) accounted for only 1.6% or less of total AUC. Almost no sulfide was excreted in the urine. The compound was transformed to its C(4)-glucuronide, a reaction common to drugs of the dioxo-pyrazolidine series. The appearance of the sulfide in plasma may be clinically important, since this metabolite shows a strong inhibitory effect on platelet aggregation in various in vitro experimental systems.

Adult↗

PubMed1982

Enhanced drug metabolism after sulfinpyrazone treatment in patients aged 50 to 60 years.

The induction of liver drug metabolism was investigated in five patients before and after the administration of 800 mg sulfinpyrazone daily for 4 weeks, by using antipyrine plasma-pharmacokinetics and by determining urinary excretion of 6-beta-OH-cortisol and serum gamma-glutamyl-transpeptidase (GGT) activity. Antipyrine half-life was shortened in all patients from a mean value of 12.3 +/- 3.9 h to 7.8 +/- 2.0 h and antipyrine clearance was increased from 39.0 +/- 16.0 ml/min to 57.6 +/- 13.7 ml/min. In contrast the volume of distribution of antipyrine was unaffected; the values being 38.0 +/- 8.6 liters and 37.4 +/- 5.7 liters, respectively. In all patients the excretion of 6-beta-OH-cortisol in the urine went up from 65.0 +/- 25.7 micrograms/24 h to 346.8 +/- 193.4 micrograms/24 h. The ratio 6-beta-OH-cortisol/free cortisol changed from 4.1 to 15.8. After 21 days of treatment the GGT increased from 17.4 +/- 4.9 units/liter to 32.6 +/- 12.5 units/liter The data presented confirm that sulfinpyrazone induces drug metabolism in patients of the older age group. Interactions between sulfinpyrazone and other drugs given simultaneously must be borne in mind.

Age Factors↗

PubMed1985

Determination of sulfinpyrazone and four metabolites in plasma and urine by high pressure liquid chromatography.

An HPLC method for the simultaneous determination of sulfinpyrazone and its p-hydroxy, sulfone, sulfide and p-hydroxysulfide metabolites in human plasma and urine samples was developed. Optimization with regard to sample preparation and chromatographic conditions was investigated. In the final procedure samples were acidified with HCl, extracted with a 1 + 1 (vol/vol) mixture of 1-chlorobutane and chloroform; urine extracts were re-extracted with citrate buffer (pH 4.5). HPLC was performed on reversed phase (RP 8) columns with a 48 + 52 (vol/vol) mixture of ethanol and citrate buffer (pH 2.5) as the mobile phase. The lower limit of detection for sulfinpyrazone and the sulfide metabolite is 10 ng/ml, for the other metabolites it is 50 ng/ml. An example of application of this procedure to pharmacokinetic studies in a volunteer receiving a single oral dose of sulfinpyrazone is given.

Chromatography, High Pressure Liquid↗

PubMed1980

High-performance liquid chromatographic analysis of sulfinpyrazone and its metabolites in biological fluids.

A rapid, senstivie, and specific high-performance liquid chromatographic method is described for the quantitative analysis of sulfinpyrazone and its sulfone and p-hydroxy metabolites in plasma and urine. The method uses two different procedures for sample preparation: (1) a rapid and convenient procedure using a single extraction with 1-chlorobutane and subsequent back-extraction into sodium hydroxide solution for the analysis of sulfinpyrazone and its sulfone metabolite, and (2) a more time consuming procedure using triple extraction with ethylene dichloride, a buffer wash, and back extraction into the base for the additional analysis of the p-hydroxy metabolite. The lower limit of sensitivity for fulfinpyrazone is 50 ng/ml. Concentrations of sulfinpyrazone between 0.05 and 0.1 and 50 micrograms/ml were measured with an average coefficient of variation of 3.9%, ranging from 1.5 to 6.1%.

Butanes↗

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↗

PubMed1983

Kinetics and metabolism of sulfinpyrazone.

Six normal subjects (three men and three women) took 200 mg sulfinpyrazone in two oral preparations, a capsule and a suspension. Plasma and urine levels of sulfinpyrazone and the sulfide, p-hydroxy, and sulfone metabolites were measured over three days. The plasma sulfinpyrazone/time concentration profiles indicated a postabsorptive biexponential decline with a mean terminal half life (t1/2) of 299 +/- 107 min. There was intersubject variation in the formation of the metabolites, the greatest being with the sulfide metabolite. Mean t1/2 of the sulfide metabolite was 659 +/- 192 min. The apparent fraction of sulfinpyrazone absorbed was 0.93 +/- 0.24 and the free fraction in plasma was 1.26 +/- 0.04%. Since the sulfide metabolite has a more potent antiplatelet effect and its formation in normal subjects is variable, direct administration of the sulfide may provide a more predictable antithrombotic effect in patients.

Absorption↗

PubMed1985

Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial.

We performed a randomized, double-blind, placebo-controlled trial in 555 patients with unstable angina who were hospitalized in coronary care units. Patients received one of four possible treatment regimens: aspirin (325 mg four times daily), sulfinpyrazone (200 mg four times daily), both, or neither. They were entered into the trial within eight days of hospitalization and were treated and followed for up to two years (mean, 18 months). The incidence of cardiac death and nonfatal myocardial infarction, considered together, was 8.6 per cent in the groups given aspirin and 17.0 per cent in the other groups, representing a risk reduction with aspirin of 51 per cent (P = 0.008). The corresponding figures for either cardiac death alone or death from any cause were 3.0 per cent in the groups given aspirin and 11.7 per cent in the other groups, representing a risk reduction of 71 per cent (P = 0.004). Analysis by intention to treat yielded smaller risk reductions with aspirin of 30 per cent (P = 0.072), 56 per cent (P = 0.009), and 43 per cent (P = 0.035) for the outcomes of cardiac death or nonfatal acute myocardial infarction, cardiac death alone, and all deaths, respectively. There was no observed benefit of sulfinpyrazone for any outcome event, and there was no evidence of an interaction between sulfinpyrazone and aspirin. Considered together with the results of a previous clinical trial, these findings provide strong evidence for a beneficial effect of aspirin in patients with unstable angina.

Angina Pectoris↗

PubMed1992

Dietary effects of allopurinol and sulfinpyrazone on development, survival, and reproduction of German cockroaches (Dictyoptera: Blattellidae).

Diets containing two gout medications, allopurinol and sulfinpyrazone, were fed ad libitum to first- or second-instar German cockroaches for 15 wk or until 100% mortality was reached. Cockroaches fed greater than or equal to 0.10% allopurinol diets weighed significantly less than those fed the control diet. Mortality of cockroaches fed diets containing greater than or equal to 0.05% allopurinol was significantly greater than those fed the control diet. The LT50 (6.1 wk) of cockroaches fed diets containing 0.10% allopurinol was significantly less than those fed any other diet containing allopurinol. LT50s and slopes were proportional and inversely related, respectively, to percentage of allopurinol in the diet. The addition of sulfinpyrazone to allopurinol diets minimally enhanced the blatticidal nature of the diets. Nymphs fed diets containing greater than or equal to 0.05% allopurinol experienced significant delays in adult emergence. Cockroaches fed greater than or equal to 0.01% allopurinol diets aborted a significantly greater percentage of their oothecae than those fed the 0.001% allopurinol or control diets. Hatched oothecae from cockroaches fed the 0.01% allopurinol diet had significantly fewer nymphs than those fed the 0.001% allopurinol or control diets. Percentage of oothecae aborted and number of nymphs per hatched ootheca from cockroaches fed a 2% sulfinpyrazone diet did not differ significantly from the control.

Allopurinol↗

PubMedDate not supplied

Influence of sulfinpyrazone on infarct size, hemodynamics, and arrhythmia following coronary occlusion in the pig.

We compared infarct size (nitroblue tetrazolium method), hemodynamic variables, and arrhythmias of a group of seven sulfinpyrazone-treated pigs (30 mg/kg/day for 7 days preoperatively, 30 mg/kg/i.v. 30 min before coronary ligation) with a control group of seven animals. Infarct size after ligation of the left anterior descending coronary artery was 20.3 +/- 1.1% in the sulfinpyrazone group and 20.3 +/- 0.5% in the control group. Heart rate, arterial blood pressure, cardiac output, and stroke volume were comparable in both groups before and for 60 min following ligation. There was no significant difference between the two groups in the number of premature ventricular contractions the PVC grade (Lown) or in the number of episodes of ventricular tachycardia or ventricular fibrillation during the 30-min observation period. We conclude that short-term administration of sulfinpyrazone has no effect on infarct size or arrhythmias in the acutely ischemic myocardium of the pig.

Animals↗

PubMed1982

Effect of sulfinpyrazone on the metabolism of arachidonic acid in isolated hamster lungs.

When 50 nmol of 14C-arachidonate was injected into the pulmonary circulation of isolated hamster lungs, the perfusion pressure was increased. This increase was not changed when sulfinpyrazone was infused into the pulmonary circulation at 20 mumol/l. Neither was the total amount of radioactivity in the effluent changed by sulfinpyrazone. The metabolites of arachidonic acid were analyzed from the nonrecirculating perfusion effluent, which was extracted with ethyl acetate first at neutral pH and then at pH 3.5. The only significant change in the metabolite formation was a small decrease in the amount of one metabolite extracted at neutral pH (obviously 12-hydroxy-5,8,10-heptadecatrienoic acid). The amounts of other metabolites, including 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and TxB2 were unchanged. The present study indicates that the pulmonary metabolism of arachidonic acid is changed only slightly by sulfinpyrazone.

Animals↗

PubMed1985

Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.

To resolve questions of drug actions, efficacy, and interactions for platelet-modifying agents used clinically, we have compared the relative capacities and mechanisms of aspirin, dipyridamole, sulfinpyrazone, and dazoxiben to prevent arterial thromboembolism in a baboon model. In 136 studies the agents were given twice daily by oral administration both singly and in combination. The antithrombotic efficacy of a given therapy was determined by its capacity to interrupt steady-state platelet utilization induced by thrombogenic arteriovenous cannulae. When given alone, dipyridamole and sulfinpyrazone reduced the rate at which platelets were utilized by thrombus formation in a dose-dependent manner with essentially complete interruption by dipyridamole at 10 mg/kg per d. In contrast, neither aspirin (2-100 mg/kg per d) nor dazoxiben (20-100 mg/kg per d) decreased cannula platelet consumption detectably despite the striking reduction in the capacity of platelets to produce thromboxane B2. However, aspirin, but not dazoxiben, potentiated the antithrombotic effects of dipyridamole and sulfinpyrazone in a dose-dependent fashion without changing the pharmacokinetics for any of the agents. Complete potentiation required aspirin at 20 mg/kg per d to be given with each dose of dipyridamole. Because dazoxiben's blockade of platelet thromboxane A2 production was not associated with antithrombotic potentiation, and because complete potentiation by aspirin required a dose that fully inhibited vascular production of prostaglandin I2 (PGI2), we conclude that aspirin's potentiating effect on dipyridamole is independent of PGI2 production or inhibition of thromboxane A2 formation. In addition, because frequent repeated and synchronous dosing of aspirin was necessary, aspirin's potentiating effects appear to be produced by mechanism(s) unrelated to its potent, irreversible inhibition of platelet cyclooxygenase.

Animals↗

PubMed1980

Sulfinpyrazone: a review of its pharmacological properties and therapeutic use.

Sulfinpyrazone1 has long been recognised as a potent uricosuric agent, but has more recently been studied extensively as a platelet inhibitor and antithrombotic agent. It is active in man following oral administration and has been reported to be effective in reducing the incidence of transient ischaemic attacks, thromboembolism associated with vascular and cardiac prostheses, recurrent venous thrombosis, arteriovenous shunt thrombosis and sudden cardiac death following myocardial infarcton. Sulfinpyrazone has not been demonstrated to be effective in preventing or reducing the risk of stroke or death in patients with cerebrovascular disease with a recent history of cerebral or retinal ischaemioc attacks. The normal total dose of sulfinpyrazone as an antithrombotic agent is 800mg daily. The drug has been used continuously for up to 4 years with no serious adverse reactions or laboratory abnormalities. There has been no apparent diminution of effect with time. Sulfinpyrazone is not a substitute for conventional anticoagulant agents (e.g. the coumarin derivatives) in the treatment of venous thrombosis, but is an important drug for the treatment of conditions associated with arterial thrombosis and possibly for the prophylaxis of recurrent venous thrombosis.

Animals↗

PubMed1990

[Effect of sulfinpyrazone on peritoneal and renal clearance in patients with chronic renal failure treated by intermittent peritoneal dialysis].

The paper was performed in order to evaluate the influence of sulfinpyrazone given orally in the doses of 400 mg to 16 uraemic patients during intermittent peritoneal dialysis on transperitoneal and renal transfer of different molecular weight substances. It was shown that sulfinpyrazone causes the increase in dialysate excretion of uric acid, sodium and protein but does not influence the transperitoneal transfer of water, potassium, creatinine, glucose, heparin and acetic acid. Renal function determined by diuresis volume as well as clearance of sodium, potassium, creatinine, uric acid and protein remained unchanged after the drug administration. Thus, when sulfinpyrazone is used during peritoneal dialysis a possibility of its action on the peritoneal membrane permeability should be taken into consideration.

Adult↗

PubMed1985

Treatment with sulfinpyrazone of essential mixed cryoglobulinemia.

Platelet production time (PPT), circulating platelet aggregates (CPA ratio) and plasma beta-thromboglobulin (beta TG) were determined in patients with essential mixed cryoglobulinemia (EMC) before and after two months' treatment with sulfinpyrazone. Sulfinpyrazone determined a clinical improvement in 8 of the 16 patients. Basal PPT and CPA ratio were reduced compared with normal values but not significantly; after sulfinpyrazone treatment both PPT and CPA ratio increased to normal levels. High plasma beta TG levels were found before and after treatment. These data suggest that in some cases of EMC there is a picture of in vivo platelet activation, but with the small number of patients it was not possible to evaluate a possible correlation between platelet hyperactivity and the clinical picture.

Adult↗

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↗

PubMed1982

Phenylbutazone and sulfinpyrazone interaction with oral anticoagulant phenprocoumon.

To compare the marked hypoprothrombinemic augmentation in man of racemic warfarin sodium by the pyrazolons phenylbutazone and sulfinpyrazone with that of the coumarin anticoagulant phenprocoumon, these interactions were studied prospectively in six normal subjects. Large single doses of racemic phenprocoumon, 0.6 mg/kg orally, were administered with and without daily phenylbutazone, 300 mg, or sulfinpyrazone, 400 mg, beginning three days before phenprocoumon and continuing for 14 days. Daily blood samples were drawn for phenprocoumon content and one-stage prothrombin time. Phenylbutazone markedly increased both the phenprocoumon concentrations and prothrombin times, whereas sulfinpyrazone did not.

4-Hydroxycoumarins↗

PubMed1981

[Acute renal failure induced by sulfinpyrazone (author's transl)].

We report on 4 cases of reversible acute renal failure (ARF), appearing within the first days after institution of a sulfinpyrazone treatment (600 mg p. day) early after a myocardial infarction. Urinary data were consistent with an acute tubular necrosis. A renal biopsy, performed in 3 patients, revealed only very discrete tubular and interstitial lesions, not helpful in the understanding of the ARF. Three pathogenetic mechanisms could be evoked. Data in favour of an acute tubular precipitation of uric acid or an immunologically induced acute interstitial nephritis are lacking. More probably this ARF is due to an inhibitory effect of sulfinpyrazone on the renal prostaglandin synthesis. Early after a myocardial infarction, renal prostaglandins could play an important protective role in maintaining the renal circulation. Renal function should be monitored closely when sulfinpyrazone is prescribed, especially early after a myocardial infarction.

Acute Kidney Injury↗