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Clinical evaluation of suprofen in the treatment of elderly patients with pain of diverse etiology.

This 4-week, open design study was conducted to evaluate the efficacy and safety of suprofen (200-1,200 mg/day) in the treatment of elderly patients with pain of diverse origin, all of whom suffered from secondary disorders. All patients reported pain of moderate to very severe intensity upon study enrollment, which improved considerably in 89% of patients by week 1. 12 of the 16 patients reported good to very good pain reduction by week 4. Suprofen was extremely well tolerated by this patient population, and there were no drug-related study withdrawals. These results show suprofen to be a potentially useful drug for the treatment of elderly patients suffering from various painful conditions.

Aged↗

Dextrans--potential polymeric drug carriers for suprofen.

Dextrans are clinically useful biodegradable polysaccharide macromolecules and have been utilized as carriers for suprofen. Conjugates of suprofen were synthesized by preparing their acylimidazol derivatives which were condensed in situ with dextrans of different molecular weights (40000, 60000, 110000 and 200000). The structures of the synthesized conjugates were confirmed by IR and NMR spectroscopy. The degrees of substitution obtained were between 7.5 and 9.0%. The molecular weight was determined by the Mark-Howin Sakurada viscosity equation. Hydrolysis was studied in different buffer solutions (pH 1.2, 7.4, 9.0) and 80% human plasma (pH 7.4) and followed first order kinetics. Much faster hydrolysis was observed at pH 9.0 compared to pH 7.4 buffer solution and 80% human plasma (pH 7.4). Biological evaluation for acute and chronic anti-inflammatory activity was performed and the results were found to be comparable with the parent drug. The ulcerogenic index of conjugates showed a remarkable reduction compared to the parent suprofen.

Animals↗

Effects of flurbiprofen and suprofen on the miotic activity of 1% acetylcholine and 0.01% carbachol.

The nonsteroidal antiinflammatory agents (NSAIAs) flurbiprofen and suprofen applied topically to reduce miosis may counteract the desired effects of miotics used during ocular surgery. In a pigmented rabbit model, 1% acetylcholine was shown to cause a greater, significant initial (for the first 30 minutes) constriction (P less than .05) than 0.01% carbachol in eyes pretreated with flurbiprofen and suprofen. From 2 to 8 hours, NSAIA pretreatment had a greater miotic effect with carbachol than with acetylcholine. There were no significant differences between flurbiprofen and suprofen on the miotic effect of carbachol or acetylcholine.

Acetylcholine↗

[The radioprotective action of suprofen].

Suprofen is a new non-steroidal anti-inflammatory drug administered intragastrically 90 min before roentgen irradiation in a dose of 20 mg/kg and then daily for 10 days in a dose of 10 mg/kg exerts the radioprotective effect evaluated according to a 30-day survival rate and an average life expectancy of the deceased animals as well as according to a decrease of postirradiation leukopenia incidence. A single administration of suprofen following roentgen irradiation exerts no radioprotective effect. Suprofen was found to enhance the radioprotective action of cysteamine.

Animals↗

[A controlled clinical single-dose comparative study of suprofen and diflunisal].

In a single-dose, double-blind randomized study, the analgesic efficacy of suprofen 200, suprofen (alpha-methyl-4-(2-thienylcarbonyl)-benzene acetic acid; Suprol) 400 mg and diflunisal 750 mg capsules was determined in comparison to placebo capsules. A total of 130 patients participated in the study, all of them requiring analgesic treatment on the first post-operative day following meniscectomy. The treatment groups were homogeneous with respect to their demographic data. With the chosen pain model all active test substances were statistically significantly superior to placebo as far as pain intensity differences (SPID), pain relief (TOTPAR) and global evaluation of efficacy were concerned. Despite great differences in dosage and half-life, the active test substances must be regarded as equipment. Side effects were reported by 2 patients each in the diflunisal 750 mg and the placebo group, and by 1 patient treated with suprofen 200 mg.

Adolescent↗

Suprofen: the pharmacology and clinical efficacy of a new non-narcotic peripheral analgesic.

Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.

Animals↗

Suprofen kinetics in healthy male volunteers after intramuscular injection of increasing dosages.

Kinetics of alpha-methyl-4-(2-thienyl-carbonyl)-phenylacetic acid (suprofen, Suprol) a non-narcotic antiphlogistic analgesic, were studied in two clinical experiments. In a bioavailability study (study A) suprofen, given as intramuscular injection was absorbed more rapidly (mean peak plasma time 20.0 min) than from the capsule formulation (mean peak plasma time 57.5 min). With respect to the amount systemically absorbed, measured as area under the plasma concentration-time curve, both dosage forms were equivalent. Individual plasma concentration profiles (study B) were described by a 2-compartmental model with a mean first order absorption rate of 0.095 min-1, a rapid mean disposition rate alpha of 0.025 min-1 and an apparent terminal plasma elimination rate beta of 0.004 min-1. There was dose-independent kinetics and a linear correlation between peak plasma concentration versus dose and area under the curve (AUC) versus dose after intramuscular injection of suprofen up to 200 mg, leading to dose proportional bioavailability data.

Adult↗

Comparative efficacy of topically applied flurbiprofen, diclofenac, tolmetin, and suprofen for the treatment of experimentally induced blood-aqueous barrier disruption in dogs.

OBJECTIVE: To compare the relative efficacies of 4 topical nonsteroidal anti-inflammatory drugs at preventing blood-aqueous barrier (BAB) disruption in dogs. DESIGN: 1 eye of each dog was treated with 1% suspensions of diclofenac, flurbiprofen, suprofen, or tolmetin, or with control solution. After 4 applications of eyedrops at 10-minute intervals, BAB disruption was induced in the treated eye by anterior chamber paracentesis. The severity of BAB disruption was measured by anterior chamber fluorophotometry. ANIMALS: 40 ocular-normal dogs. PROCEDURE: After pretreatment with eyedrops, rapid 100-microliters nonleaking anterior chamber paracentesis was performed in 1 eye of each dog to induce BAB disruption. 1 day after paracentesis, 1 ml of 10% fluorescein sodium was injected i.v.. The amount of fluorescein entering the anterior chamber of each eye was measured 30 to 60 minutes later by use of a computerized scanning fluorophotometer. The degree of BAB disruption was determined by comparing the amount of fluorescein entering the aqueous humor of the paracentesed eye with that of the nonparacentesed eye. RESULTS: At postparacentesis day 1, the order of statistically significant BAB-stabilizing efficacy among groups was: diclofenac > flurbiprofen > suprofen > tolmetin = control solution. CONCLUSIONS: Topically applied 1% suspensions of diclofenac, flurbiprofen, and suprofen are effective at preventing BAB disruption after paracentesis in dogs, indicating their potential usefulness for treatment of prostaglandin-mediated ocular disease. 1% tolmetin is no more effective than control solution.

Animals↗

Suprofen, a potent antagonist of sodium urate crystal-induced arthritis in dogs.

A standardized sodium urate-induced arthritis test in dogs is described in detail. A microcrystalline suspension of 20 mg/ml in 0.9% NaCl was injected into one of the stifle joints in a volume of 0.5 ml and motor impairment of the dogs was scored every 30 min over a period of 8 h. A direct quantitative comparison was made of the anti-arthritic activity of acetyl-salicylic acid, phenylbutazone, indometacin and alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen). All compounds were given by oral gavage immediately after the sodium urate injection. Among the compounds studied suprofen was the most potent antagonist of sodium urate-induced arthritis in dogs. Comparing the ED50 values suprofen was about 4 times as potent as indometacin, 9 times as potent as phenylbutazone and 60 times as potent as acetyl-salicylic acid.

Animals↗

The effects of suprofen in rats with implanted cotton pellets.

Implanted cotton pellets with closely adherent granuloma tissue were removed from rats treated orally during 7 consecutive days with solvent or 2.5, 5.0, 10, 20 or 40 mg/kg of alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) by gavage. Highly significant decrease (P less than 0.001) of the total cotton pellet dry weight was observed in the groups given 5.0 mg/kg of suprofen or more. The pronounced activity on total cotton pellet weight was obtained without any effect on body weight gain, on food consumption or on the weight of thymus and adrenal glands in the same animals. We conclude that a maximal effect against the proliferative phase of inflammation is obtained with 10 mg/dg of suprofen, in the absence of any steroid-like or toxic side-effect.

Adrenal Glands↗

High-performance liquid chromatographic assay for suprofen, a potent new analgesic, in plasma.

A simple, rapid, high-performance liquid chromatographic (HPLC) determination of therapeutic levels of suprofen, a potent new analgesic, in human plasma is described. After a simple extraction, the compound is analyzed by HPLC using a reversed-phase column and a UV detector. Quantitation is accomplished using an external standard; peak areas are determined by computer. An average recovery of 80.0 +/- 8.5% SD of the drug was obtained over the 0.2-20.0-microgram/ml range. Maximum sensitivity is approximately 0.1 microgram/ml. No interference is encountered from any known metabolite of suprofen.

Chromatography, High Pressure Liquid↗

A clinical trial of Suprofen and aspirin in post-operative dental pain.

A double-blind trial comparing the analgesic efficacy of Suprofen 200 mg with aspirin 750 mg was carried out on 120 patients. There was no statistical difference between the two, though Suprofen had fewer side effects and could be used in circumstances where aspirin is contra-indicated.

Adolescent↗

The epidemiology of the acute flank pain syndrome from suprofen.

Suprofen, a new nonsteroidal anti-inflammatory drug, was marketed in early 1986 as an analgesic agent. Until physicians began reporting an unusual acute flank pain syndrome to the spontaneous reporting system, 700,000 persons used the drug in the United States. Through August 1986, a total of 163 cases of this syndrome were reported. To elucidate the epidemiology of the syndrome, a case-control study was performed, comparing 62 of the case patients who had been reported to the spontaneous reporting system to 185 suprofen-exposed control subjects who did not have the syndrome. Case patients were more likely to be men (odds ratio, 3.8; 95% confidence interval, 1.2-12.1), suffer from hay fever and asthma (odds ratio, 3.4; 95% confidence interval, 1.0-11.9); to participate in regular exercise (odds ratio, 5.9; 95% confidence interval, 1.1-30.7), especially in the use of Nautilus equipment (p = 0.02); and to use alcohol (odds ratio, 4.4; 95% confidence interval, 1.1-17.5). Possible risk factors included young age, concurrent use of other analgesic agents (especially ibuprofen), preexisting renal disease, a history of kidney stones, a history of gout, a recent increase in activity, a recent increase in sun exposure, and residence in the Sunbelt. These were findings that were suggestive but did not reach conventional statistical significance. These findings are consistent with the postulated mechanism for this unusual syndrome: acute diffuse crystallization of uric acid in renal tubules.

Acute Kidney Injury↗

Absorption and excretion of suprofen in both sexes of rats, guinea pigs, and rabbits.

DL-2-(4-2-Thienylcarbonyl)phenyl)propionic acid (suprofen) was rapidly absorbed in both sexes of rats, guinea pigs, and rabbits after oral administration. Blood levels after a single dose of 2 mg/kg 3H-suprofen in all the animals reached maxima within 15 min, and elimination of the 3H from blood was rapid; the radioactivity was mostly excreted in the urine and feces within 24 h after dosing.

Administration, Oral↗

Autoradiographic study on the distribution of suprofen in rats of both sexes.

The tissue distribution of 14C-labeled DL-2-(4-(2-thienylcarbonyl) phenyl) propionic acid (suprofen) after po administration was studied in male, female, and pregnant rats by whole-body autoradiography. 14C localized rapidly in such highly vascularized tissues as liver, kidney, and lung as well as heart in rats of both sexes, but no significant uptake was found in the central nervous system. About half of the 14C in the liver and kidney was found to be unchanged suprofen; smaller amounts of 2-(4-(2-thienylhydroxymethyl)phenyl)propionic acid and 2-(4-carboxyphenyl)propionic acid were also detected. In pregnant rats, a low level was found in the uterus and placenta; the drug penetrated the fetuses to only a limited degree. No appreciable radioactivity was found in rat tissues 24 h after dosing.

Administration, Oral↗

Suprofen-related nephrotoxicity. A distinct clinical syndrome.

We describe a unique clinical syndrome of flank pain and acute renal failure that is associated with suprofen, a nonsteroidal anti-inflammatory drug that has recently been made available in the United States. In the initial 6 months of the drug's distribution in this country, at least 16 patients developed this syndrome. All 16 had acute flank pain and 13 developed mild reversible renal failure within 12 hours of ingestion of one to three suprofen capsules. This syndrome is unlike other nephrotoxic syndromes related to nonsteroidal anti-inflammatory drugs. The mechanism is not known.

Abdomen↗

Effects of suprofen on renal function in patients with rheumatoid arthritis.

Suprofen is a new potent analgesic with antiinflammatory properties that appears to inhibit prostaglandin synthetase in a tissue-selective manner, having relatively little effect on the kidneys of experimental animals. The effects were studied of one week of treatment of rheumatoid arthritis patients with suprofen or ibuprofen on Na+ and K+ excretion, creatinine clearance, urinary enzymes that are markers for tubular damage, and urinary prostaglandins such as PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin). Neither compound caused changes in renal function related to the week of treatment, but significant decreases in prostaglandins were observed: this change was fully reversible after discontinuation of the drug.

6-Ketoprostaglandin F1 alpha↗

Open study of the clinical effect of suprofen drops in children.

Antipyretic effect, tolerability, and acceptance of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) drops were tested within the scope of an open study including a total of 111 children with fever of various etiology; two investigational centers participated in this study. The initial mean rectal temperature averaged 39.3 degrees C. The dosage of suprofen drops depended upon the patient's body weight and age; the drug was administered up to q.i.d., for 4 days at the longest. Body temperature, pulse rate, and respiratory rate were recorded prior to administration and 1/2, 1, 1 1/2, 2, 3, 4, 5 and 6 h after first administration of the drug. The antipyretic effect of the treatment was appreciated good in 89% of the cases. Reduction in temperature was statistically significant at all rating times after first administration of the drops as compared with the initial values. Adverse drug experiences such as vomiting and loose stools were seen in only 5 cases. The tolerability was considered good in 96% and the acceptance in 94% of the cases.

Body Temperature↗