PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Sulindac”

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 19 recordsLinked to original sources
PubMed1986

Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac.

Nonsteroidal antiinflammatory drugs impair renal function in susceptible patients with cirrhosis and ascites. A new antiinflammatory drug, sulindac, is reported not to affect renal function. To evaluate its renal-sparing mechanism, sulindac was administered for 5 days and ibuprofen for 1 day to 10 patients and paraaminohippurate and inulin clearances, serum and urine eicosanoids, and serum and urine sulindac metabolites were monitored. Ibuprofen reduced renal clearances in the 5 subjects with greatest sodium retention, whereas sulindac had no effect. Plasma concentration of the active sulfide metabolite was markedly increased in liver patients, and this concentration correlated with the inhibition of serum thromboxane (r = 0.75, p = 0.01). The percent inhibition of serum thromboxane with sulindac administration correlated with the inhibition of urinary eicosanoids (r = 0.68-0.81, all p less than 0.02). Ibuprofen was generally a more potent inhibitor of serum and urine eicosanoids. Thus, a major factor in the renal-sparing effect of sulindac appears to be its less potent inhibition of renal and extrarenal cyclooxygenase systems.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Sulindac and indomethacin suppress the diuretic action of furosemide in patients with cirrhosis and ascites: evidence that sulindac affects renal prostaglandins.

Nonsteroidal anti-inflammatory drugs (NSAID) suppress prostaglandin-dependent renal blood flow and furosemide-induced diuresis in patients with cirrhosis and ascites. Since sulindac may selectively spare inhibition of renal prostaglandins, we evaluated the interactions of acute administration of sulindac or indomethacin with furosemide in 15 patients with cirrhosis and ascites. Prior to furosemide, indomethacin reduced creatinine clearance (by 55%), urinary volume (by 82%), sodium (by 93%), and prostaglandin E2 (by 87%) (all P less than 0.05), whereas sulindac had no effect. However, both drugs reduced furosemide-induced diuresis. Indomethacin appeared slightly more potent in reducing the diuresis (55% v 38%), natriuresis (67% v 52%), and prostaglandin E2 (PGE2) release (81% v 74%). In a similar protocol in healthy subjects, furosemide-induced diuresis and natriuresis were also blunted by both drugs. Thus, under conditions of enhanced prostaglandin activity from furosemide, sulindac does affect renal function. These data suggest that renal function should be monitored in patients with cirrhosis and ascites who receive sulindac as well as other NSAID.

Anti-Inflammatory Agents↗
PubMed1979

Sulindac in ankylosing spondylitis. Double-blind evaluation of sulindac and indomethacin.

Ankylosing spondylitis affects about 1% of the population. In the past, evaluation of therapy in the management of this disease has been hampered by the lack of availability of objective criteria for following the condition. By using recently developed measurements of spinal mobility and other variables we have compared sulindac, a recently introduced nonsteroidal antiinflammatory drug, and indomethacin in a double-blind six-month parallel study of 30 patients. Sulindac and indomethacin have comparable efficacy and tolerance. Advantages of sulindac include a twice-a-day dose regimen.

Double-Blind Method↗
PubMed1990

Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis.

PURPOSE: The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function. PATIENTS AND METHODS: In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness. RESULTS: Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl-beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index. CONCLUSION: The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

A kinetic study of sulindac in the elderly.

To study the disposition of the anti-inflammatory drug sulindac, its active sulphide metabolite, and the inactive sulphone metabolite, sulindac (200 mg twice daily) was given to eight elderly subjects for at least 14 consecutive days. The drug was then ceased for 72 hours, and suitable samples were collected to study its elimination. The mean steady-state concentration for sulindac was 5.0 micrograms/ml, for sulindac sulphide was 6.5 micrograms/ml, and for sulindac sulphone was 13.2 micrograms/ml. These are approximately twice the reported steady-state levels for the respective redox forms in healthy young adults. The mean half-lives of sulindac, sulindac sulphide, and sulindac sulphone were 18.3 hours, 22.3 hours, and 54.6 hours, respectively. One patient who had mildly abnormal liver function tests developed more severe abnormalities whilst receiving sulindac. These returned towards normal after cessation of treatment. This patient had the highest steady-state plasma concentration of sulindac sulphone. It is concluded that care should be taken with the use of sulindac in the elderly, and control of patients' symptoms should be attempted with lower doses of the drug before the standard dose of 200 mg twice daily is administered.

Age Factors↗
PubMed1985

Nonsteroidal anti-inflammatory effect of sulindac sulfoxide and sulfide on gastric mucosa.

Gastric injury resulting from nonsteroidal anti-inflammatory drugs is thought to require direct contact of the drug with the gastric mucosa. An inactive form of a drug (as a prodrug) should protect against mucosal damage. Because sulindac sulfoxide has little effect on prostaglandin synthesis until it is reduced to sulindac sulfide after absorption, we performed a double-blind, crossover endoscopic study in 15 normal subjects to compare the prodrug sulindac sulfoxide (200 mg b.i.d.), the active sulfide metabolite sulindac sulfide (100 mg b.i.d., which yields similar sulfide blood concentrations), a positive control (aspirin, 650 mg q.i.d.), and a negative control (placebo). Each drug was taken for 1 week and gastric mucosa were endoscopically assessed before and after 2, 5, and 7 days of dosing. Aspirin predictably damaged the gastric mucosa, whereas the effects of sulindac sulfoxide and sulindac sulfide could not be distinguished from those of the placebo. We conclude that sulindac sulfoxide as a prodrug is not directly responsible for the reduced severity of gastric mucosal lesions. Both sulindac sulfoxide and sulindac sulfide are poorly soluble in acid gastric contents and the reduced damage may relate to the inability of high concentrations of the drug to enter gastric mucosal cells.

Administration, Oral↗
PubMed1985

Sulindac hepatotoxicity: effects of acute and chronic exposure.

Sulindac (Clinoril), an anti-inflammatory drug increasingly used in Australia for the treatment of rheumatological conditions, is unpredictably associated with a cholestatic hepatitis. We present three cases of sulindac hepatitis. The first case exemplifies acute sulindac hepatitis, the second, continuously exposed to sulindac for 18 months, had chronic sulindac hepatotoxicity, and in the third case, the long-term histological outcome after cessation of sulindac is described. The clinical, biochemical, and histopathological characteristics are those of a cholestatic hepatitis which resolves on withdrawal of the drug. We report marked anisonucleosis with cytoplasmic invaginations into the nucleus and binuclearity of hepatocytes as additional histological features of sulindac hepatitis. There is no evidence that sulindac hepatitis progresses to irreversible structural liver damage, although nuclear changes may persist for up to two months after cessation of the drug. The clinical and biochemical features of all reported cases of sulindac hepatitis are summarised.

Adult↗
PubMed1982

Effects of sulindac on in vitro immunologic function and on prostaglandin production by human peripheral blood mononuclear leukocytes.

Prostaglandins (PG) appear to regulate immune-mediated inflammation, but the mechanisms involved remain unclear. Several families of nonsteroidal antiinflammatory drugs (NSAID) have been observed to inhibit PG synthesis. Among these drugs, sulindac sulfide is a potent inhibitor of PG production while its parent pro-drug, sulindac sulfoxide (sulindac), lacks PG synthesis inhibitory activity in cell-free systems. We have studied the effects of sulindac sulfoxide on the blastogenic response of human peripheral blood mononuclear cells (PBMC) stimulated by exposure to alloantigens and mitogens in vitro. Sulindac inhibited proliferation of activated PBMC in a dose-dependent manner but had little effect on the proliferation of unstimulated cells. The inhibition of mitogen-induced blastogenesis correlated with both the uptake of radiolabeled drug and the inhibition of in vitro production of PG (PGE and PGF) by mitogen-activated PBMC. These data indicate a functional relationship between PG synthesis and immune cell activation which may also apply to PBMC activated in vivo by autoimmune disease. Metabolism of sulindac sulfoxide by PBMC in vitro produced too little sulindac sulfide to adequately explain the inhibition of PG production. These data suggest that immunomodulation by sulindac may be due to a direct inhibition of cellular activation. Thus, it is proposed that decreased PG production may be a result rather than the cause of the hypoproliferative response.

Dose-Response Relationship, Immunologic↗
PubMed1988

Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2-receptor antagonists (cimetidine or ranitidine) in human volunteers.

The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.

Adult↗
PubMed1992

Effects of sulindac and oltipraz on the tumorigenicity of 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone in A/J mouse lung.

The efficacies of the non-steroidal, anti-inflammatory drug sulindac and the schistosomicidal agent oltipraz in inhibiting lung tumorigenesis was measured in A/J mice. Lung tumors (15.7 tumors/mouse) were induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 9.1 mg/mouse) administered in drinking water for 7 weeks. Feeding mice with sulindac (123 mg/kg diet), 2 weeks before carcinogen treatment until they were killed reduced tumor multiplicity by 53%. Oltipraz (250 mg/kg diet), however, has no effect on tumorigenesis. The absorption and metabolism of NNK were compared in the stomachs and intestines isolated from mice fed AIN-76A diet or sulindac + diet. Sulindac had no effect on alpha-carbon hydroxylation, pyridine N-oxidation or carbonyl reduction of NNK. Mouse lung explants were cultured with 4.7 microM [5-3H]NNK for 4 or 8 h. The addition of 1 mM sulindac to the culture medium reduces the alpha-carbon hydroxylation and pyridine N-oxidation of NNK. However, the administration of sulindac in the diet prior to the excision of the lung explants had no effect on these two metabolic pathways. We compared the levels of sulindac and its sulfide and sulfone metabolites in the lungs, livers and plasma of mice fed an AIN-76A diet containing 130 mg sulindac/kg for 2 weeks. The sulfide metabolite was the most abundant of the three compounds in plasma (17.6 pmol/microliters) and liver tissues (17.7 pmol/mg) but it could not be detected in lung tissues. These results show that non-steroidal anti-inflammatory drugs constitute a new class of chemopreventive agents in lung tumorigenesis. The tumor chemopreventive activity of sulindac is not mediated by the sulfide metabolite responsible for its anti-inflammatory activity.

Adenoma↗
PubMed1990

Multicentre double-blind study of the efficacy, safety and tolerance of pirazolac compared with sulindac in patients with rheumatoid arthritis.

Of the 160 patients (80 pirazolac/80 sulindac) who entered the study through 14 investigators, three-quarters completed a 12-weeks therapy and three-fifths completed the entire 24-weeks therapy. In the pirazolac group 15% of the patients and in the sulindac group 11% dropped out from the study due to adverse clinical experience. The drop-out rates due to unsatisfactory therapeutic response were respectively 15% and 16% in the pirazolac and the sulindac groups. Both treatment groups showed significant improvement from baseline for all parameters except for the erythrocyte sedimentation rate at weeks 4, 8, 12 and 16 for the sulindac group and weeks 4 and 8 for the pirazolac group. The two treatment groups were comparable as to effectiveness; however, the improvement rates in 36 out of 41 efficacy measurements based on the definition of clinically relevant changes in relation to baseline were estimated to be superior for the group under pirazolac therapy. The rate of improvement for the American Rheumatism Association functional class at the end of the study was 23% in the pirazolac group and 9% in the sulindac group (p less than 0.05). Of the patients in the pirazolac and sulindac groups, 45% and 44% respectively reported no adverse effects at all throughout the whole 24-weeks study. The rates of patients reporting at least one adverse reaction in a body system were not different between the two groups. An exception was the body as a whole where ten patients (12.5%) in the sulindac group and only two (2.5%) in the pirazolac group reported adverse reactions (p = 0.03). No differences occurred between the two treatment groups with regards to intensity, causality or the number of occurrences of adverse clinical experiences. One death in the sulindac treatment group was reported during the study. In both treatment groups, alterations in laboratory tests were minor or negligible or associated with abnormal pre-treatment values and, generally speaking, without any clinical relevance. There were some patients, who had increases from baseline in alkaline phosphate in both treatment groups. However, these were usually transient, occasionally complemented by a slight increase of serum glutamic oxaloacetic acid transaminase.

Adult↗
PubMedDate not supplied

Effect of uremia and anephric state on the pharmacokinetics of sulindac and its metabolites in rats. I. An application of pharmacokinetic model for reversible metabolism.

Plasma levels of sulindac and its metabolites, sulfide and sulfone, were measured in normal, uremic, and anephric rats following concurrent administration of 11C-sulindac and 3H-sulfide (5 mg-eq/kg). A marked decrease in plasma concentration of sulfide was found in uremic rats, while sulindac concentration in these rats was unchanged. In contrast, anephric rats cleared sulindac more slowly than control rats, but had no effect on the sulfide. A pharmacokinetic model for reversible metabolism was used to characterize the kinetic parameters for sulindac----sulfide interconversion system. The intrinsic clearances of unbound drug were calculated for the interconversion and elimination processes. The results indicated that the reduction of sulindac to sulfide is impaired in uremic and anephric rats. The oxidation of sulfide to sulindac was increased in uremic rats, but decreased in anephric rats. Experimental uremia caused a decrease in plasma protein binding of sulindac and sulfide and an increase in the apparent volumes of distribution of the redox species. Anephric state has less effect on plasma protein binding and volume distribution.

Animals↗
PubMedDate not supplied

Effect of dimethyl sulfoxide on sulindac disposition in rats.

Sulindac and dimethyl sulfoxide (DMSO) are both effective antiinflammatory agents in man. Since the sulfoxide moiety in these compounds is metabolized similarly, a biochemical interaction between the two drugs in vivo was thought to be possible. After iv injections of sulindac (5 mg/kg), plasma concentrations of sulindac, and its sulfide and sulfone metabolites, were measured in normal rats and in rats that had received, 30 min earlier, a single ip dose of DMSO (0.1, 0.5, or 1.0 ml). The half-life of sulindac (normally 94 min) was increased significantly by DMSO (0.1, 0.5, or 1.0 ml). The half-life of sulindac (normally 94 min) was increased significantly by DMSO (408 min after 1.0 ml of DMSO). Plasma sulfide metabolite levels were reduced in a dose-related manner by DMSO (93% reduction in peak concentration after 1.0 ml of DMSO). Sulfone metabolite concentration was also significantly diminished by the highest dose of DMSO. Similarly, DMSO was shown to decrease conversion of sulindac to sulfide and sulfone metabolites by rat liver enzymes in vitro. Sulfoxide reductase was more sensitive to DMSO inhibition than was sulfoxide oxidase both in vivo and in vitro. These data demonstrate that DMSO can significantly alter in vivo the formation of the pharmacologically active, sulfide metabolite of sulindac; therefore, concurrent use of DMSO and sulindac should be approached with caution.

Animals↗
PubMed1987

Analysis of sulindac and metabolites in plasma and urine by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method with ultraviolet detection is described for the quantification of sulindac, sulindac sulfone and sulindac sulfide in plasma and sulindac, trans-sulindac, sulindac sulfone and sulindac sulfide in urine. Plasma samples are de-proteinized with acetonitrile and urine samples are injected directly following enzymatic hydrolysis of glucuronide metabolites. The resulting chromatograms are essentially free from endogenous interference and the limits of detection are 0.1 microgram/ml for plasma and 0.2 microgram/ml for urine for all of the above compounds.

Chromatography, High Pressure Liquid↗
PubMed1985

Sulindac is not renal sparing in man.

We investigated the claimed renal-sparing effect of the cyclooxygenase inhibitor sulindac. Fifteen normal women following a diet of 50 mEq salt a day were randomly assigned to 5 days of either placebo, sulindac, 200 mg b.i.d., or indomethacin, 25 mg q.i.d., after first serving as their own controls. Renal effects were assessed by the excretion rate of prostaglandin (PG) E2 (an index of renal PG synthesis), sodium balance, plasma renin activity (PRA), and the response to furosemide. Systemic effects were assessed by collagen-induced platelet aggregation and thromboxane B2 formation and by the urinary excretion of a systemically formed metabolite of PGF2 alpha (PGF-M). Both sulindac and indomethacin resulted in a positive sodium balance and a reduction in 24-hour urinary PGE2 excretion (range -49% to -86%). Basal PRA was decreased by indomethacin only, but the increases in PRA and in urinary PGE2 excretion in response to furosemide were inhibited by both sulindac and indomethacin. Sulindac reduced the natriuresis induced by furosemide, and indomethacin reduced the rise in inulin clearance after furosemide. Thus the two nonsteroidal anti-inflammatory drugs had similar effects on the kidney. Indomethacin had a greater effect than sulindac on the inhibition of collagen-induced platelet aggregation and thromboxane synthesis and the two drugs had equivalent effects on the reduction of PGF-M excretion. Peak plasma drug concentration of indomethacin (1.9 +/- 0.4 microgram/ml) and sulindac sulfide (7.7 +/- 1.9 microgram/ml) were those associated with clinical efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Acute renal effects of sulindac and indomethacin in chronic renal failure.

The effects of 2 days of oral dosing with sulindac (200 mg twice a day) or indomethacin (75 mg twice a day) on glomerular filtration rate, urinary excretion of prostaglandin E2, sodium homeostasis, and other renal function parameters were investigated in eight patients with chronic stable impaired renal function. Indomethacin reduced creatinine clearance (from 41.0 +/- 7.9 to 30.3 +/- 6.3 ml/min) and increased serum levels of creatinine and beta 2-microglobulin. Sulindac had no effect on any of these parameters. Both drugs induced depression of urinary prostaglandin E2 excretion; this depression was greater after indomethacin. Urinary sodium excretion fell from 144.4 +/- 18.7 to 85.5 +/- 9.7 mmol/24 hr after indomethacin and from 131.7 +/- 11.6 to 103.4 +/- 13.3 mmol/24 hr after sulindac. Body weight increased 1.2 kg after indomethacin but was not changed by sulindac. Plasma renin activity was reduced from 2.3 +/- 0.8 to 1.7 +/- 0.6 nmol/L/hr by sulindac and from 2.8 +/- 0.8 to 1.5 +/- 0.5 nmol/L/hr by indomethacin. Urinary N-acetyl-beta-glucosaminidase and kallikrein excretion was not changed by either drug. Our data suggest that sulindac affects renal prostaglandin E2 synthesis and sodium excretion in patients with severe renal failure to a lesser extent than does indomethacin. Sulindac still seems to be the drug of choice in this group of patients, but glomerular filtration rate, body weight, and electrolyte balance should be carefully monitored.

Acetylglucosaminidase↗
PubMed1987

Biotransformation of sulindac in end-stage renal disease.

In normal humans sulindac, a prodrug, undergoes two major biotransformations: irreversible oxidation to the inactive sulfone metabolite and reversible reduction to the pharmacologically active sulfide metabolite. To assess any effect of end-stage renal failure on sulindac biotransformation, six patients were given 200 mg sulindac orally. Plasma was sampled over 24 hours. Protein binding of sulindac and metabolites was determined by equilibrium dialysis. Results were compared with historic controls. AUC(0-12) for sulindac and the sulfone were similar to controls. AUC(0-12) for the sulfide was significantly reduced to 4.85 micrograms X hr/ml from 13.1 micrograms X hr/ml (P less than 0.02). Protein binding of all three compounds was significantly reduced by renal failure. When corrected for protein binding, the AUC(0-12) for sulindac and the sulfone was twice that of controls whereas that of the sulfide was 42 ng X hr/ml compared with 83 ng X hr/ml in normal individuals (P less than 0.001). This suggests that end-stage renal failure impairs the reduction of sulindac to the active sulfide whereas oxidation to the sulfone is intact.

Administration, Oral↗