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At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

Individual variability in concentrations of urinary sulindac sulfide.

Among 70 patients with arthritis who were receiving satisfactory maintenance therapy with sulindac (300 to 400 mg daily), 64% had no detectable sulindac sulfide (active metabolite) in one to four random urine specimens. However, 36% had 1.0 to 7.8 (mean, 2.2 +/- 1.4) micrograms/ml sulindac sulfide in urine, similar to the therapeutically effective concentrations found in 24 concurrent plasma specimens (1.4 to 9.0 micrograms/ml). Ten patients had sulindac sulfide in only one or two of two to four urine specimens. Thus, 36% of the patients had pharmacodynamically significant concentrations of sulindac sulfide in urine, presumably capable of suppressing the cyclooxygenase pathway responsible for prostaglandin synthesis in the kidney and elsewhere. The findings suggest individual variability in the capacity for renal oxidation of sulindac sulfide to inactive metabolites, perhaps related to genetic or environmental factors or both. These findings may help to explain conflicting reports on the effects of sulindac on urinary prostaglandins and renal function.

Adult↗
PubMed1992

Randomized comparative trial of indomethacin and sulindac for the treatment of refractory preterm labor.

This study was designed to investigate the efficacy and safety of sulindac in the treatment of preterm labor. Thirty-six women in preterm labor who had failed initial attempts at tocolysis with magnesium sulfate were randomized to receive either oral indomethacin or oral sulindac for 48 hours. The mean gestational ages at admission were 29 and 30 weeks for the sulindac and indomethacin groups, respectively. There was a significantly greater hourly fetal urine output, deepest amniotic fluid pocket, and amniotic fluid index in the sulindac group. A trend toward higher fetal ductus arteriosus flow velocities noted in the indomethacin group was not seen in the sulindac group. The drugs had similar success in delaying delivery for 48 hours or 7 days. The mean birth weights were 2000 and 2323 g for the sulindac and indomethacin groups, respectively. Sulindac appears to be as effective as indomethacin for refractory preterm labor but with fewer fetal side effects.

Adult↗
PubMed1991

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1992

Effect of sulindac on prostaglandin synthesis in human and in cultured rat renal and vascular smooth muscle cells.

To examine the hypothesis that sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of sulindac and other nonsteroidal anti-inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1977

On the question of an interaction between sulindac and tolbutamide in the control of diabetes.

The effect of sulindac and tolbutamide on the control of diabetes was studied in 12 tolbutamide-treated maturity-onset diabetics with stable glycemic control. After one week of hospitalization on a metabolic ward for adjustment of diet and activity, the patients were treated with sulindac, 200 mg twice daily for one week. The time-to-peak plasma tolbutamide concentration was 3.1, 3.1, and 3.2 hr, respectively, after tolbutamide alone, after the first dose of sulindac, and after sulindac for a week. The areas under the plasma tolbutamide curve were 23.68, 22.10, and 22.78 for the same periods. The half-life for plasma tolbutamide was 7.46, 7.15, and 7.38 hr, respectively. None of the differences were statistically significant. The mean fasting plasma sugar was lower after the sulindac treatment (from 12.5 to 112.9 mg/100 ml, p less than 0.05), but the postprandial values increased slightly (from 137.7 to 142.6). It was concluded that there was no clinically significant interaction between sulindac and tolbutamide.

Adult↗
PubMed1977

A multicenter trial of sulindac in osteoarthritis of the hip.

Sulindac (cis-5-fluoro-2-methyl-l-[(p-methyl sulfinyl)-benzylidene]-indene-3-acetic acid) is a new nonsteroidal antirheumatic drug recently evaluated in a double-blind trial of 91 patients with hip osteoarthritis. Consecutive patients with documented flare following previous drug withdrawal were randomly assigned to one of 3 treatment groups: (1) sulindac given twice daily, (2) sulindac given 4 times daily, and (3) placebo. The dosage of sulindac, 100 to 300 mg daily, was adjusted according to patient global response and tolerance at 3- to 7-day intervals over 3 wk. Of 15 efficacy measurements evalulated, there was no difference between sulindac given 2 or 4 times daily, but differences were disclosed between one or both sulindac treatment groups and placebo in 11 of the 15 efficacy measurements (p less than 0.05, less than 0.01). The frequency of adverse reactions was of the same order for each treatment group. These included gastrointestinal upset, rash, and dizziness, usually transient and mild to moderate in severity. Serial laboratory studies revealed no evidence of renal, hepatic, or hematopoietic toxicity.

Adult↗
PubMed1979

A controlled clinical study comparing sulindac with ibuprofen and aspirin in the treatment of musculo-skeletal diseases.

Forty-six patients (seventeen male, twenty-nine female) with musculo-skeletal disease were put on a controlled clinical study comparing sulindac with ibuprofen and soluble aspirin. Twenty patients were treated with sulindac 200 mg twice daily, twelve received sulindac 100 mg twice daily, eight had ibuprofen 400 mg thrice daily and six treated with soluble aspirin 600 mg thrice daily. All patients did well on these drugs, but the ones on sulindac 200 mg twice daily showed better response than sulindac 100 mg twice daily. It proved to have the same efficiency as ibuprofen and soluble aspirin; but had less side-effects and also patients required to take the drug only twice daily to get relief because of its prolonged duration of action.

Adolescent↗
PubMed1977

The disposition of sulindac.

The disposition of sulindac, a new nonsteroid anti-inflammatory drug, has been studied in normal volunteers in five separate clinical studies. Based upon material balance considerations, a minimum of approximately 88% of an oral dose is absorbed. The major biotransformations involve irreversible oxidation of the sulfinyl group of sulindac to sulfone and reduction to the corresponding sulfide. The latter, which all available evidence indicates to be the pharmacologically active form of sulindac, is not excreted in urine, and has an apparent terminal half-life of 18.2 hr, well suited to twice daily dosage of its pro-drug. Following twice daily dosage of sulindac for 5 days, plasma levels of sulfide approach an apparent steady state with concentrations varying only within a twofold range over each dosage interval. The reversible biotransformation between sulindac and its active sulfide metabolite provides the basis for two therapeutic advantages relating to the gastrointestinal intolerance usually associated with anti-inflammatory drugs: (1) circumvention of initial exposure of gastric and small intestinal mucosa to the active form of the drug and (2) maintenance of systemic levels of active drug by means of enterohepatic recycling, principally of inactive pro-drug.

Adult↗
PubMed1977

Identification of the biologically active form of sulindac.

In five animal species, the only quantitatively significant biotransformations undergone by cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl) benzylidene]indene-3-acetic acid (sulindac) are oxidation of its sulfinyl substituent to sulfone, and reduction to sulfide. The former metabolite is eliminated unchanged and elicits no pharmacological response. The sulfide, on the other hand, is readily reoxidized in vivo to sulindac. In each of seven in vivo models of inflammation, sulfide administered as such is more active than sulindac. The inference that the activity of sulindac might be attributed in whole or in part to the sulfide was tested directly by comparison of responses with concentrations of each reduction oxidation species in appropriate biological fluids. Regression analyses of circulation levels of sunlindac and sulfide vs. inhibition of rat paw edema, and of their levels in synovial fluid vs. response in the dog knee joint assay, show highly significant correlations only for sulfide. Sulindac thus appears to be a "latentiated" or "pro-drug," oral dosage with chich may circumvent the gastrointestinal side effects commonly associated with nonsteriod anti-inflammatory agents.

Administration, Oral↗
PubMed1979

A double-blind, crossover trial of mefenamic acid, sulindac and flurbiprofen in rheumatoid arthritis.

A double-blind crossover trial was carried out in 24 patients to compare the effects of mefenamic acid, flurbiprofen, sulindac and placebo. Each drug was given for 2 weeks, the treatment sequence being randomized. Daily doses were 1500 mg mefenamic acid, 150 mg flurbiprofen or 150 mg sulindac. All of the active drugs were significantly superior to placebo in terms of pain score, patients' assessment, articular index of joint tenderness, and duration and severity of morning stiffness. There was improvement in grip strength compared with placebo, but the differences were not statistically significant with sulindac. There was slight reduction in joint circumference but this was only statistically significant in the right hand with flurbiprofen and sulindac. No significant differences were found in technetium uptake in knee joints. The three drugs appeared to be equally effective and tolerated, and no significant differences were noted.

Adult↗
PubMedDate not supplied

[Sulindac suppositories: treatment of pain in osteoarthritis (author's transl)].

Thirty one patients with osteoarthritis (29 hips, 16 knees) were submitted to a treatment with sulindac at a daily dose of 200 mg bid suppositories during four weeks. This trial showed that the treatment brought relief of pain in the majority of patients. Compared with others previously prescribed drugs, sulindac was more effective (72%). Sulindac suppositories were well tolerated; only three drop-out because side-effects (gastro intestinal tract: 2, skin 1) have been reported. Sulindac suppositories tolerance was reported as good.

Adult↗
PubMed1976

Intestinal blood loss after a new anti-inflammatory drug, sulindac.

Sulindac was tested for fecal blood loss in 40 healthy male subjects whose red cells had been labeled with Na2 51 CrO4. Two daily dose levels of 240 mg and 400 mg were compared with 4.8 gm of aspirin and placebo for 2 wk. At day 15, aspirin-induced blood loss was greater than that of both dose levels of sulindac and of placebo (p less than 0.05). There were no significant differences between the two sulindac groups and the placebo group. Aspirin caused more adverse reactions than sulindac, 240 mg (p less than 0.05), 400 mg (p less than 0.05), and placebo (p less than 0.05).

Adult↗
PubMed1976

[Sulindac: Clinical test of a new antiinflammatory agent in rheumatoid arthritis (author's transl)].

Sulindac, a new non steroidal antiinflammatory agent has been compared with acetylsalicylic-acid in a six week controlled double blind study in 28 patients with rheumatoid arthritis. In continuation of this study all patients have been treated with Sulindac up to 18 months. Sulindac has proved to be statistically significant superior to acetylsalicylic-acid as regarding the achieve of pain during the day, of morning stiffness, of gripping of the right hand and evaluation of patients response to the drug. Moreover markedly fewer adverse reactions especially of the gastrointestinal tract were seen. During the following long term study, when 19 patients were treated with Sulindac, a further statistically significant improvement of all controlled parameters up to the complete relief of complaints was observed. A reduction of the daily dose could be established. Laboratory evaluations as well as controlls of EKG and blood pressure showed no evidence of any organ toxicity of this drug.

Adult↗
PubMed1991

The effects of sulindac and diclofenac in essential hypertension controlled by treatment with a beta blocker and/or diuretic.

A placebo-controlled, double blind crossover study of the non-steroidal anti-inflammatory drugs (NSAIDs) sulindac and diclofenac was conducted in 16 patients with essential hypertension that was controlled by treatment with a beta blocker, a diuretic or co-administration of both. In 4 cases, another antihypertensive agent (prazosin or verapamil) was also co-administered. In every patient, plasma creatinine concentration was less than 0.14 mmol/l (normal range 0.07-0.12 mmol/l). Sulindac and diclofenac were each given for 7 weeks. Diclofenac caused a decrease of borderline significance in plasma aldosterone concentration. Neither NSAID altered the mean values for systolic or diastolic blood pressure, body weight, plasma electrolyte concentrations, urate clearance, creatinine clearance or plasma renin activity. However, rises in plasma creatinine concentration and falls in creatinine clearance occurred during NSAID therapy in three individual subjects. No significant differences were observed in this study between the effects on renal function or blood pressure of sulindac and diclofenac, both of which appear not to interfere with the antihypertensive actions of beta blockers and diuretics.

Adrenergic beta-Antagonists↗
PubMed1992

A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis.

The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.

Aged↗