Clinically controlled comparative study of intravenous single doses of suprofen versus indoprofen.

The analgesic effects of single intravenous doses of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) 200 mg/ml and alpha-4-(2-isoindolinyl-2-one)-phenylpropionic acid (indoprofen) 200 mg were compared within the scope of a randomized single-blind study. The test population consisted of 87 patients for whom analgesic treatment was indicated as soon as severe to major pain set in following meniscectomy or disease of a ligament. The treatment groups were homogeneous with respect to demographic data and intensity of pain prior to treatment. In the pain models chosen both drugs resulted in rapid pain relief within 15 min following their application. As to decreased intensity of pain (SPID) and pain relief (TOTPAR), the results obtained 2 h after the test were with indoprofen statistically significantly superior to those obtained with suprofen. The investigator's global appreciation of effectiveness revealed no intergroup differences. Therapeutic results were seen in 95.5% of the subjects on suprofen and in 97.6% of those on indoprofen. The tolerability of suprofen was very good in 95.3% of the cases on suprofen and in 97.3% of those on indoprofen. Four patients in the suprofen group experienced adverse reactions that were, however, not drug related.

Controlled single-blind clinical study of suprofen syrup versus metamizole syrup.

The analgesic effect and the tolerability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) syrup 200 mg and metamizole syrup 500 mg were compared in a randomized single-blind study including hospitalized patients with severe to moderate chronic pain. The 2 treatment groups consisted of 30 subjects each and were homogeneous as to the demographic data. Pain intensity was appreciated by the investigator prior to the treatment and on days 2, 3, and 5 of the study; pain relief was assessed on days 2, 3, and 5 of the therapy. Although pain intensity was on treatment with suprofen more markedly reduced than with metamizole, there was no statistically significant difference between the 2 treatment groups (chi 2-test). The Mann-Whitney test revealed that on days 3 and 5 pain relief with suprofen was significantly superior to that with metamizole. According to the investigator's final global evaluation, suprofen syrup 200 mg had very good to good effect in 70% of the cases, whereas the effectiveness of metamizole was rated good to very good in 44%. Side-effects manifesting themselves as gastric irritation and nausea were recorded for 3 patients on suprofen and 2 subjects on metamizole.

Double-blind placebo-controlled study of the efficacy and tolerability of suprofen suppositories in patients with osteoarthritic pain.

In a placebo-controlled double-blind trial analgesic effectiveness and tolerability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) 300 mg suppositories were evaluated for 45 informed patients suffering from chronic pain due to osteoarthritis; the subjects were treated rectally, t.i.d., for 10 days. Suprofen proved to be statistically significantly superior to placebo in all the variables considered for evaluation of the analgesic effect, i.e., pain intensity and relief scores, sum of pain intensity differences (SPID), total pain relief (TOTPAR), global assessments by investigator and patient. In particular, the efficacy of suprofen was judged by the physician good or very good in 86.3% of the patients. Similar frequencies of rectal side-effects were observed in both treatment groups, with slightly but not significantly higher incidence in the group treated with suprofen. Haematologic and clinical chemistry laboratory tests showed no statistically significant alterations due to the treatment.

Open clinical study with suprofen drops in the treatment of postoperative and posttraumatic pain.

Analgesic effect and tolerability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) drops were tested in an open study including 51 informed outpatients with moderate to severe postoperative and posttraumatic pain. Suprofen drops were administered for 7 days, at doses of 33 drops (= 200 mg of suprofen) t.i.d. or q.i.d. The pain intensity was recorded prior to the treatment and after 2, 4 and 7 days; pain relief was assessed on days 2, 4 and 7. Effectiveness and tolerability were by the investigator and by the patients globally evaluated upon completion of the trial. The intensity of pain dropped within the 7-day treatment period from initially severe pain to mild. Pain relief was seen in 92% of the subjects after day 2, in 98% after day 4, and in 100% after day 7 of treatment. Investigator's and patients' final evaluation of the therapeutic effect indicated good analgesic activity in 86% of the population, and very good analgesic effect in 84%. Moderate effect was seen in 12 and 14%, respectively. The tolerability of suprofen drops was by investigator and patients considered good to very good in 82% of the cases, moderate in 16%, and poor in 1 case.

Clinical experience and results of treatment with suprofen in pediatrics. 5th communication: a single-blind study on antipyretic effect and tolerability of suprofen syrup versus metamizole drops in pediatric patients.

In a single-blind study, 60 children in two age groups (30 patients: 6 months to 3 years; 30 patients: 3 years to 12 years), were orally treated with either alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol), syrup 10 mg/ml or metamizole drops 50% for a maximum period of 4 days, up to 4 times a day. The children presented with high fever due to bacterial or virus infections. Body temperature, pulse rate, and respiratory rate were evaluated at the beginning and then 30 min, 1, 1 1/2, 2, 3, 4, 5, and 6 h after the first administration of the respective drug. Significant differences between the drugs were found for all variables; this demonstrated that with suprofen the antipyretic effect set in more rapidly than with the reference drug. No side-effects were observed in children treated with suprofen syrup. Two patients showed adverse effects, i.e. sweating and hypotension, during the treatment with metamizole. Due to its good antipyretic effect and good tolerability, suprofen appears to be particularly useful for symptomatic treatment of pediatric patients with fever caused by bacterial or virus infections.

Suprofen sustained release kinetics in healthy male volunteers. 1st communication: a single dose open crossover bioavailability study of suprofen sustained release tablets versus capsules.

An open crossover study was performed in 12 healthy male volunteers to compare the bioavailability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) 600 mg sustained release tablets versus the suprofen capsule (2 X 200 mg). The pharmacokinetic profiles in plasma and urine were determined by a HPLC assay. In the dose range studied, the two suprofen formulations were not associated with any clinically significant effects on the blood pressure, heart rate or ECG. The results of the physical and neurological examinations showed no abnormal results. The results of haematology, clinical chemistry and urinalysis also showed no significant modifications. However, increased serum creatinine values were observed in some volunteers following suprofen administration. A drug relationship to this finding cannot be excluded with certainty. Two volunteers complained of nausea and vomiting following administration of two suprofen capsules. For this reason, volunteer no. 9 was withdrawn by the investigator from the study and replaced by an eligible substitute. In general, single doses of the two suprofen formulations investigated, were subjectively and objectively well tolerated. From the suprofen plasma-concentration time profiles, it was apparent that, whilst the elimination of suprofen was similar for both formulations, there was a marked delay in absorption of the tablet formulation. This formulation resulted in statistically significantly later maximum plasma levels and longer mean residence time (p less than 0.001). In comparison to the reference capsule formulation, the tablet had statistically significantly lower (75%) bioavailability. Measurement of suprofen concentrations in the urine indicated that less than 1% of the administered dose was excreted by this route.

Suprofen sustained release kinetics in healthy male volunteers. 2nd communication: a multiple dose steady-state kinetics of suprofen sustained release tablets during 6 days in healthy male volunteers.

To 12 healthy male volunteers, who had given their consent, 11 administrations of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) sustained release tablets 600 mg were given twice a day with a dosage interval of 12 h. It could be demonstrated that suprofen given as multiple dose application of sustained release tablets was well tolerated. Effective mean plasma levels were reached after the second dosage. There was no indication of accumulation nor accelerated elimination during the 6-day period. There was no statistically significant difference between the mean plasma curve after the last administration of the 6-day period and the mean plasma curve after the 3rd application. Also the AUC's in the respective intervals turned out not to be statistically significantly different from each other. Clinical and laboratory tests showed no clinically relevant deviations from the normal range. No adverse reactions whatsoever were observed.

Double-dummy comparison of suprofen and indometacin sustained release formulations.

In a randomized double-dummy study a new dosage form of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol), i.e., suprofen sustained release 600 mg tablets, was compared with indometacin sustained release 75 mg capsules. The test population included 60 hospitalized subjects in severe chronic pain requiring analgesic treatment. The treatment groups were homogeneous as to their anamnestic data. Treatment was given for 3 weeks; the drugs were uniformly administered in the morning and in the evening. The intensity of pain was assessed using a visual analog scale (VAS) prior to administration of the first dose on day 1 of the therapy, and then for up to 10 h. Further assessments of pain intensity and pain relief were obtained after 1, 2, and 3 weeks of therapy. Comparison of the mean pain intensity (VAS) at the individual rating times revealed statistically significant better pain relief with suprofen than with indometacin already 1 h after the administration (p less than 0.05, multivariate analysis of variance). This statistically significant difference as compared with indometacin was confirmed at all subsequent time points. The weekly assessments of pain intensity showed that the results obtained with suprofen were superior to those with indometacin, although they were not statistically significant. However, pain relief after 2 weeks' treatment with suprofen was significantly superior (p = 0.0061, exact test) to the result observed with indometacin. The results obtained with suprofen in weeks 1 and 3 were superior to those with indometacin, but they were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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

The aim of the study was to test the antipyretic effect and the tolerability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) syrup in a sample of pediatric patients with fever of various etiology. The study was designed as an open multiple dose study including 41 hospitalized children (males and females) aged 6 months to 12 years. Temperature, pulse rate, and respiratory rate were measured immediately after consumption of the syrup, after 30 min, 1 h, 1 1/2, 2, 3, 4, 5, and 6 h. The study was performed at one investigational center. At the end of the study, data were evaluated for a total of 41 patients. 27 patients were 5 years or less, 14 patients were 6 to 12 years old. The mean age of the males (23 patients) was 4.5 years; the mean age of the females (18 patients) was 3.8 years. There was no significant sex dependence of the development of temperature, the pulse rate, and the respiratory rate. Prior to treatment the mean temperature was 38.6 degrees C. Temperature decreased to 37.7 degrees C within 1 h and to 37.2 degrees C within 2 h after treatment. From then on, the temperature increased to 37.7 degrees C at the end of the observation period. The decrease in temperature (compared to baseline) was significant throughout the trial. The mean pulse rate decreased from 131.2/min to 119.9/min within 1 h, and to 114.0/min within 2 h. At the end of the trial the mean pulse rate was 120.1/min.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Clinically controlled comparative study of suprofen, pentazocine, and placebo. Experience with intramuscular single doses.

Analgesic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenylacetic acid (suprofen, Suprol) 200 mg were compared with pentazocine 30 mg and placebo in 88 patients in moderate to severe postoperative pain. The trial was designed as a randomized single-blind study; the test drugs were in single doses (1 ml ampuls) administered by deep intragluteal injection in the upper outer quadrant. The test population was homogeneous as to anamnestic data; the initial intensity of pain was comparable in all three groups. Statistical analysis of the obtained data revealed that at the rating times 30 min to 3 h suprofen was statistically significantly superior to placebo, while after 2 h it was significantly superior to pentazocine. The investigator's final global appreciation of effectiveness states moderate to good effect in 86% of the patients on suprofen, 76% of those on pentazocine, and 63% of the subjects on placebo. Significant difference existed only between suprofen and placebo. Systemic tolerability was considered good to very good in 97% of the subjects in all three treatment groups, whereas local tolerability was considered poor in 2 patients (6.9%) in the group on suprofen. There were no significant differences between the medications. Two subjects each on suprofen and pentazocine and 1 patient on placebo experienced side effects.

Clinical experience and results of treatment with suprofen in pediatrics. 4th communication: Assessment of pain in babies and infants/Analgesic effect of suprofen syrup in otitis media.

In a study including a total of 175 children, ranging in age from 3 months to 3 years and suffering from otitis media, the analgesic effect of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) syrup was compared with that of lidocaine 0.03 g/6 g + phenazone (phenyl-dimethylpyrazolone) 0.03 g/6 g (L PDP) ear drops. The study was designed as an open controlled trial. The test medications were applied in single doses: suprofen 5-7.5 mg/kg b.w., orally; (L PDP) 1 drop, locally. The severity of pain was assessed in the beginning of the treatment and 2 h following administration of the drugs. The results were indicative of the fact that in children on suprofen syrup marked pain relief was obtained, whereas the painful condition of children on L PDP ear drops even deteriorated.

Clinical effect of rectal application of suprofen in children. An open controlled study.

Antipyretic effect, tolerability, and acceptance of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) suppositories were tested in an open study including 90 hospitalized children with fever of various etiology. The mean rectal temperature prior to treatment was 39.3 degrees C. The dose regimen was chosen depending upon the body weight: Up to 4 suppositories were administered for maximally 4 days. Body temperature as well as pulse and respiratory rates were recorded prior to insertion of the suppository and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h following first application of the preparation. Regardless of sex and age the temperature was reduced in 85.5% of the cases; as compared to the initial values this reduction was after first application statistically significant at all rating times. The only adverse reaction - vomiting - was seen in 3 cases.

Clinical experience and results of treatment with suprofen in pediatrics. 1st communication: Suprofen dosage for children/An open and a double-blind study with suprofen syrup.

The antipyretic effect of single doses of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) syrup, administered at dose levels of 1, 2, 3, 4, 5, 7.5, and 10 mg/kg b.w., was tested in a randomized double-blind and a subsequent open study. The test populations consisted of 100 children in the double-blind study and 40 patients in the open test (20 subjects/group). The patients' age ranged from 2 to 12 years; the lowest initial rectal temperature was 39.0 degrees C. The treatment groups were homogeneous as to demographic data. The temperature was reduced in all treatment groups. In the double-blind study the mean value dropped under the subfebrile threshold of 38.0 degrees C only in the group on 5 mg/kg and remained then constant for up to 6 h following administration. No sufficient antipyretic effect was obtained with lower doses. The results of the additional open study with doses of 7.5 and 10 mg/kg indicated good antipyretic effect. This effect was not, however, superior to that obtained with 5 mg/kg. Pulse and respiratory rates returned to normal within 1.5 h following administration, except in patients on 1 mg/kg. A total of 10 patients, homogeneously distributed in the treatment groups, experienced vomiting as an adverse reaction. Short-term hypotonia was seen in one subject on 7.5 mg/kg. The results obtained show that single doses of suprofen upward of 5 mg/kg b.w. exert satisfactory, long-lasting, antipyretic effect on children.

Clinical experience and results of treatment with suprofen in pediatrics. 2nd communication: Use of suprofen suppositories as an antipyretic in children with fever due to acute infections/A single-blind controlled study of suprofen versus paracetamol.

The present randomized single-blind trial was performed to study antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) suppositories versus paracetamol (acetaminophen) suppositories in pediatric patients with fever of various etiology. The study included a population of 120 patients ranging in age from 2 to 12 years; the subjects' mean rectal temperature was 39.3 degrees C in the beginning of the therapy. The dosage of the suppositories depended upon body weight; medication was applied up to 3 times a day. The temperatures were recorded 0.5, 1, 1.5, 2, 3, 4, 5, and 6 h after the preparation was first applied. Pulse rates and respiratory rates were measured at the same rating times. The antipyretic effect of suprofen in younger patients was from 1 through 6 h (except at 3 h) statistically significantly superior to that of paracetamol. In older children, the differences in favor of suprofen were statistically significant only at 1 and 2 h after application of the drug. After the treatment pulse and respiratory rate dropped in both age groups on either treatment. The means were within the normal range at all rating times. The only adverse reaction was vomiting; this phenomenon occurred in 4 cases, i.e., in 2 cases each on either drug.

Clinical experience and results of treatment with suprofen in pediatrics. 3rd communication: Antipyretic effect and tolerability of repeat doses of suprofen and paracetamol syrup in hospitalized children/A single-blind study.

Antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol), syrup and paracetamol (acetaminophen) were compared within the scope of the present randomized single-blind study; the test population included a total of 115 children ranging in age from 6 months to 12 years. All patients were admitted to the hospital with an average temperature of 39.3 degrees C, their disease being caused by bacterial or viral infections. The dose levels for treatment with syrup depended upon the children's age and body weight. Treatment was in most cases given for two days; a three-times-a-day schedule was used. The (rectal) temperature as well as pulse and respiratory rates were measured prior to treatment and 0.5, 1, 1.5, 2, 3, 4, 5, 6 h after first administration of the test preparations. The results showed that the antipyretic effect of suprofen was in both age groups at all rating times statistically significantly superior to that of paracetamol. Pulse and respiratory rates dropped in both age groups after treatment; the means were within the normal range at all rating times. Adverse drug reactions were seen in 5 patients on suprofen and in 3 cases on paracetamol. It is, however, questionable whether such reactions are drug-dependent.

Antipyretic effect and tolerability of suprofen suppositories. Controlled clinical double-blind study with placebo.

The aim of the present study was to investigate the antipyretic effect of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) 300 mg suppositories compared to placebo in patients with fever of various etiology. The trial was designed as a randomized double-blind study including 30 patients per treatment group. After insertion of the suppository, temperatures were measured after 30 min, 1, 2, 3, 31/2, 4, 5, and 6 h. The study was performed at four investigational centers. At the end of the study, a total of 61 patients could be evaluated: 27 on suprofen, 34 on placebo. There were no statistically significant differences in the anamnestic data. The mean age of the subjects on suprofen was 66.5 years, and on placebo 61.3 years. Prior to treatment, the mean temperatures in the two treatment groups were 38.8 and 38.9 degrees C, respectively. In the suprofen group, the temperature dropped to a mean of 37.9 degrees C within 3 h and to 37.6 degrees C within 6 h. The decrease in temperature was less marked in the placebo group; here the mean temperature was 38.4 degrees C after 3 h and 38.2 degrees C after 6 h. Suprofen was found to be superior to placebo throughout the study, the differences being statistically significant after 3 h up to 6 h. The only side effect experienced by a subject on suprofen was vomiting.

Pharmacokinetics and tolerability of suprofen. Experience with intramuscular application in healthy volunteers.

In the present randomized single-blind study local and systemic tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) 200 mg/ml i.m. were compared with those of diclofenac 25 mg/ml and placebo. The three treatment groups consisted of 15 patients each and were homogeneous with respect to demographic parameters. The volunteers were assigned to these groups in random fashion and underwent treatment with 3 injections/day of either suprofen or diclofenac or placebo for 7 days. Mild local pain or systemic intolerance signs were equally rare in all three groups. The laboratory tests with the three preparations studied failed to indicate any negative influence on the hematopoietic organs or the adrenal activity. Abnormal changes in the ECG and the cardiovascular parameters during the treatment were not observed. Moderately or slightly elevated SGOT and SGPT values were seen during treatment with suprofen; however, these values returned to normal after the treatment. As compared with these elevations the values for subjects on diclofenac were higher and did not return to normal within 5 days following withdrawal of the drug. Moreover, the creatine phosphokinase activity, observed in both the suprofen and the diclofenac group, was so extremely high in subjects on diclofenac that this drug had to extremely high in subjects on diclofenac that this drug had to be withdrawn on day 4 of the study. On the basis of these results it can be stated that intramuscular injections of suprofen 200 mg/ml are locally and systemically well tolerated even on administration t.i.d. Measurement of the steady-state plasma level was not indicative of altered kinetic behaviour of suprofen. The plasma levels remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Local and systemic tolerability of suprofen. Experience with intravenous administration and infusion in healthy volunteers (1st comm.).

Local and systemic tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol 200 mg/ml intravenous injection and suprofen 200 mg/ml infusion were in the present single-blind crossover study assessed and compared with those of placebo i.v. 12 volunteers each were in random fashion assigned to one of the three treatment groups; for a period of 7 days the subjects received daily 2 intravenous injections or infusions of suprofen or placebo, respectively. Investigator and patients appreciation of local tolerability revealed that no pain or discomfort occurred in 98% of the subjects on suprofen and in 100% of those on placebo. The incidence of limited, moderate or mild, adverse reactions was in the suprofen group higher than in the placebo group. The laboratory tests for the treatment groups indicated no negative effects on either the hematopoietic organs or the liver function; no abnormal changes in ECG and cardiovascular parameters were observed during the treatment period. Tests of the renal parameters, i.e., creatinine clearance, creatinine, and urea (BUN), revealed negative shifts in the first two parameters, whereas BUN remained uninfluenced. On the basis of these results it can be stated that 200 mg/ml of suprofen, given either as intravenous injection or as infusion, were both locally and systemically well tolerated even on administration b.i.d. The more or less unfavorable shifts in the renal parameters, which occurred with placebo as well as with suprofen, require further investigation.

Local and systemic tolerability of suprofen. Experience with intravenous administration and infusion in healthy volunteers (2nd comm.).

12 healthy male volunteers who had given consent to the study each received in a randomized cross-over design 13 applications of 2-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) injection solution 200 mg/ml at 8 a.m. and at 2 p.m. as i.v. bolus injections or as infusions. It could be demonstrated, that suprofen given as multiple dose i.v. bolus injections or as multiple infusion doses was well tolerated. The peak plasma concentrations after i.v. bolus injections were in the range of 16.3 to 42.3 micrograms/ml (mean 26.5) and after 2 h between 1.3 and 9.8 micrograms/ml (mean 3.2). 1.5 h after the start of infusion (end of the infusion) the plasma concentrations were in the range of 4.0 and 11.2 micrograms/ml (mean 7.2) with a infusion rate of 4.6 mg/min for the first 30 min and then of 1.1 mg/min for about 57 additional min. At 2.5 h after the infusion applications the mean plasma level was 2.0 micrograms/ml. There was no indication of accumulation nor accelerated elimination during the 7-day period. There was no statistically significant difference between the plasma elimination after the last injection of the 7-day period and the plasma elimination after i.v. single injection as well as from the elimination after the last infusion of the 7-day period.