European Journal of Rheumatology and Inflammation

Online ISSN: 0140-1610
Publications
Article
Tenoxicam is a thienothiazine derivative with anti-inflammatory properties. Due to its long half-life (40-90 hours) the drug can be administered once daily. One-hundred patients with tendinitis or bursitis were allocated in a double-blind study comparing 20 mg of tenoxicam to 20 mg of piroxicam. Both drugs were administered once daily for a period of 15 days. Clinical evaluations were performed before, on the third and seventh days of therapy and after treatment. The parameters evaluated were: spontaneous pain, tenderness, pain on movement, swelling and functional limitation. Laboratory examinations were performed prior to and at the end of the therapy. Efficacy was considered excellent or good in 42 patients of each group, moderate in six treated with tenoxicam and in four with piroxicam and poor in two with tenoxicam and four with piroxicam. Statistical evaluation was based on the Wilcoxon and U-test. No significant differences were observed between the groups. Nausea of mild intensity occurred in four cases of the tenoxicam group and in one of the piroxicam group.
 
Article
Thirty patients were allocated in a double-blind study comparing piroxicam 20 mg to tenoxicam 20 mg. Both drugs were administered once daily, before breakfast, for a period of 6 months. Clinical evaluations were performed weekly during the first 6 weeks and then monthly. The following parameters were evaluated: Ritchie articular index, pain on movement, pain at rest, grip strength, functional status, and morning stiffness. Laboratory examinations were performed before, on the 42nd day and on the 6th month of therapy. Efficacy was considered favourable in 10 cases treated with tenoxicam and in 12 with piroxicam and poor in five treated with the former and in three with piroxicam. Three patients of each group presented side effects of slight intensity. Considering the good results seen in the patients receiving tenoxicam, the treatment was maintained in nine cases for a further period of 6 months. Eleven other patients from the piroxicam group also received tenoxicam for a further period of 6 months. The efficacy was maintained in all 20 patients. Regarding adverse reactions, one patient complained of abdominal pain in the twelfth month of therapy and another patient had a brief episode of meteorism in the ninth month.
 
Article
Twenty-six patients with gonarthrosis or coxarthrosis were entered in a double-blind study to compare tenoxicam 20 mg and piroxicam 20 mg. Both groups were statistically comparable prior to treatment regarding age, sex and clinical parameters. Both drugs were administered as a single daily 20 mg dose before breakfast for a period of six months. Clinical evaluations were performed monthly. The following parameters were considered: spontaneous pain, pain on movement, pain after a day of normal activity, tenderness, flexion in degrees, time to walk 10 metres, and functional status. Laboratory examinations were performed at baseline, in the third month, and at the end of therapy. Statistical analysis was based on the Student t-test and Chi-square test. Efficacy was considered excellent or good in seven patients treated with tenoxicam and in six with piroxicam, moderate in six tenoxicam and four piroxicam patients, and poor in three patients on piroxicam. No statistical differences were observed between the two groups for the final evaluation of efficacy. Side-effects appeared in three piroxicam patients: epigastric pain, dizziness and headache in one patient, epigastric pain in another case, and one patient with urticaria. Only one patient in the tenoxicam group experienced side-effects which presented as epigastric pain of mild intensity. No laboratory alterations were observed during and at the end of treatment.
 
Article
The aim of this study was to determine the efficacy and tolerance of tenoxicam (Ro 12-0068) versus piroxicam in patients with ankylosing spondylitis. The analgesic and anti-inflammatory activity of tenoxicam and piroxicam was measured for diurnal pain, nocturnal pain, pain on movement, maximum period of immobility tolerated when seated, morning stiffness, hand-floor distance and Schober index. In all except the last two parameters, improvement with tenoxicam was statistically significant, but there was no statistical difference between the two treatments. Slight side-effects were observed in one patient in the tenoxicam group and three in the piroxicam group.
 
Article
Efficacy and toleration of piroxicam suppositories 20 mg, given once daily for 4 weeks were assessed in 96 patients suffering from degenerative joint disease and 20 patients suffering from rheumatoid arthritis. The mean scores of objective parameters measured (tenderness, swelling, limitation of movement) decreased significantly 2 and 4 weeks after initiation of therapy. Patients' self-evaluation of pain and stiffness also significantly improved during the trial. Overall evaluation of efficacy and toleration were excellent or good in more than 80% of patients. Local toleration was excellent in all but two patients.
 
Article
This paper contains a detailed account of the results obtained in 1629 patients with osteoarthritis treated with indoprofen, a recently introduced non-steroidal anti-inflammatory drug. Several traditional objective variables were selected for evaluation of efficacy, and they were shown to be highly correlated. After four weeks' treatment with doses of indoprofen ranging in the great majority of cases from two to four 200 mg tablets daily, highly significant improvement of pain was observed along with amelioration of joint motion as measured with a new arthrogoniometer specially developed for the trial. On a 5 point semiquantitative scale, pain severity decreased on the average ofrom 2.31 (0.03 S.E.M.) to 0.66 (0.02); knee flexion increased on the average from 71.8 (2 . 00) degrees to 93.0 (1.74) (p less than 0.001). These results have confirmed on a much larger scale the conclusions of phase 2 studies. The multiclinic trial disclosed more adverse reactions than those found in phase 3 studies, thus confirming that phase 4 studies are more suitable for supplying information on the acceptance of drugs by practising physicians. The risk/benefit ratio turned out to be very favourable on account of the acceptable frequency of adverse reactions which were mainly confined to the gastrointestinal tract and forced withdrawal in only 6.0% of patients. Untoward clinical events were validated with a new algorithm: their relationship with the drug was in 51.5% probable and 35.6% definite. The results of this study have confirmed the usefulness of indoprofen in the treatment of osteoarthritis.
 
Article
18,888 patients with chronic or extra-articular rheumatic diseases were treated for an average period of 36.1 or 26.9 days with the new non-steroidal anti-rheumatic agent piroxicam. In particular, piroxicam had a positive effect in terms of providing relief from pain. Side effects were relatively rare and seldom required discontinuation of treatment. In about 75% of the patients the maintenance dose was 20 mg piroxicam in a single daily dose. No influence on the laboratory values or accompanying diseases were observed.
 
Article
The long-acting antiphlogistics tenoxicam (Ro 12-0068, Tilcotil) and piroxicam in single daily oral doses of 20 mg are compared in a double-blind, group-comparative, randomised trial planned to last for five years. Results of 12 months' treatment of 108 patients with osteoarthritis of the hip or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three-quarters because of inefficacy or intolerance. Only six patients were withdrawn between 12 and 24 months, three for lack of efficacy, two for side-effects and one for reasons unrelated to therapy. There was no difference between the treatment groups with regard to incidence, time or reason for withdrawal, and only small, insignificant differences in efficacy and tolerability. This trial shows that long-term treatment of osteoarthritis with tenoxicam and with piroxicam is beneficial. Once efficacy and tolerability have been established, maintenance of therapy is feasible.
 
Article
A multicenter study, involving 850 physicians (rheumatologists and orthopedists) and 3,309 patients with osteoarthritis was carried out to prepare an epidemiological survey of this disease, and to assess the efficacy of the new non-steroidal anti-inflammatory agent, piroxicam. This drug was administered to every patient in a single daily dose of 20 mg taken after dinner for 40 days. In our patient profile, the number of women was almost double the number of men. Most patients were between the ages of 50 to 59 years. The knee was the most frequently affected joint, primarily on the right side. Obesity did not seem to play an important role in provoking the arthritic disease in these patients (only 26.6% were obese). The majority had the disease from 25 to 60 months. Arterial hypertension was the most frequent concomitant disease. No association between this or other concomitant diseases could be linked to any specific joint involvement. The efficacy of the treatment was evaluated on the 20th and 40th days after treatment was begun. On admission, pain severity in 2,065 patients (62.4%) was classified as severe, and on the 20th day of evaluation this number fell to 105 patients (3.2%), showing a dramatic reduction in pain severity during the administration of the drug. The presence of a concomitant disease did not affect either the onset or level of therapeutic response. In the final evaluation, 1,441 patients (44.4%) were classified as excellent, and 1,341 (41.4%) as good, with a total of 85.8% of patients falling into one of these two categories. This is a highly satisfactory result in the evaluation of the efficacy of an anti-inflammatory agent. Most adverse reactions involved the gastrointestinal tract, followed by the central nervous system, cutaneous, and cardiovascular manifestations. Adverse reactions were present in 462 (13.96%) on the 20th day of evaluation, and in 110 (3.37%) on the 40th day of evaluation. Fifty-two patients needed to have their treatment discontinued because of severe reactions on the 20th day of evaluation and 13 on the 40th day of evaluation. This epidemiological study of 3,309 patients is the largest ever conducted in Brazil and in all of South America. It is also the only study in which the same anti-inflammatory drug was used in very patient in the same dosage.
 
Article
An open non-comparative study was conducted to assess the efficacy and tolerability of piroxicam in patients with acute musculoskeletal disease. A total of 3011 patients of both sexes, aged between 18 and 70, were treated with piroxicam: 4 capsules (40 mg) after dinner, on the first two days and two capsules (20 mg) on the following days. Patients were evaluated for a maximum period of 14 days. Assessment of efficacy was made including local pain and limitation of mobility. The patients' self-assessment of pain was also analyzed. A clear improvement in each of the parameters analyzed was found by the third day of treatment. The general self-assessment of efficacy by the patients presented excellent and good results in 97.5%; very similar to the final assessment of efficacy made by the doctors, 91.1%. Adverse reactions were found in 368 patients (12.22%).
 
Article
Efficacy and safety of piroxicam 20 mg nocte and fenbufen 600 mg nocte were assessed in a placebo-controled cross-over comparison in thirty-nine osteoarthritic patients. When compared with placebo, piroxicam showed highly significant pain relief morning, afternoon and evening throughout the study. Fenbufen showed significant relief of morning pain only. There was a significantly and sustained relief of night pain with piroxicam compared with placebo, but no difference with fenbufen compared with placebo. This was confirmed by a statistical analysis directly comparing the results obtained for the two agents. Both piroxicam and fenbufen were well tolerated and produced markedly less side-effects than placebo.
 
Article
A single oral dose of fenbufen 900 mg was administered to 12 elderly volunteers, average age 81 years. The plasma levels of fenbufen and its major metabolites were measured at intervals over 72 hours following dosing. Results were compared with previously obtained data from young healthy volunteers. No significant differences were seen, after corrections from body weight, between the two groups for fenbufen and 2 of its metabolites. The mean serum levels in the elderly of biphenylacetic acid were significantly higher at 36 hours and 48 hours than the means at these times in the young group. This was not thought to be clinically significant. The terminal half lives for fenbufen and its major metabolites were not significantly prolonged compared with young volunteers.
 
Article
A young woman with systemic lupus erythematosus developed portal hypertension and pulmonary hypertension. This is the first report of such a case. We suggest that the presence of the lupus anticoagulant may have been related to the development of these two unusual features of her illness.
 
Article
The absorption and disposition of ibuprofen was investigated in seven hemodialyzed uremic patients. Ibuprofen (400 mg) was orally administered to each patient 1 hr or 4 hr prior to hemodialysis. Uremic patients appeared to absorb ibuprofen at a slower rate as compared to normal subjects. The hemodialysis systems used in this study yielded a mean extraction efficiency of 16.7% for ibuprofen, with a mean dialysis plasma clearance of 22.7 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the ingested dose of ibuprofen (less than 4%). The half-life of ibuprofen (1.3-1.9 hr) was not significantly altered by hemodialysis. Observations of extraction efficiency, drug recovery and half-life during dialysis suggested nondialyzability of ibuprofen, probably due to its extensive protein binding (approximately 90%). Uremic patients may require a comparatively longer time to achieve the therapeutic concentration attained in normal volunteers. However, dosage adjustment is not required once a regimen is implemented in uremia.
 
Article
The effectiveness, safety and acceptability of indoprofen (IP) and acetylsalicylic acid (ASA) were assessed in patients with osteoarthritis, in a double-blind comparative trial. Each patient received IP 600 mg/day or ASA 2100 mg/day for a four-week period; after a one-week wash-out period, the same drug was given at a higher dosage (IP 800 or ASA 2800 mg/day) for another four weeks. Seventeen patients on indoprofen and 14 on SAS completed the trial. A significant improvement was obtained with indoprofen in the different parameters measuring pain, from the first treatment period; results were similar at the end of the second period. Results with ASA, at both dosages, appeared less impressive. Two patients on indoprofen and five on ASA complained of side effects.
 
Article
This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess the efficacy and tolerability of a new, locally acting, transcutaneous flurbiprofen preparation (flurbiprofen LATTM, Boots Company PLC) in the treatment of scapulohumeral periarthritis. The new preparation consists of a nonwoven polyester patch supporting a mentholated formulation containing flurbiprofen 40 mg. Eighty patients suffering from the acute, painful phase of scapulohumeral periarthritis entered the trial, three of which failed to provide follow-up data. Each patient applied one patch every 12 hours for the 14 day trial period. Efficacy was assessed in terms of reduction of pain, improvement in shoulder movement and overall clinical assessment of the severity of the condition after treatment. Statistically significant improvements from baseline were observed in both treatment groups, with a constant overall trend in favour of flurbiprofen. The differences between the two treatment groups, however, did not reach statistical significance.
 
Article
Thirty out-patients with rheumatoid arthritis aged from 3 yrs. (+/- 0.5 SEM) were included in a between-patient controlled trial comparing effectiveness and safety of flurbiprofen 300 mg daily and indomethacin 150 mg daily. The duration of the treatment was nine weeks. Both drugs allowed to reduce the initial dose of corticosteroids administered (-21% on flurbiprofen and -12% on indomethacin) and were effective in improving clinical signs of the disease such as number of swollen joints, grip strength, articular index and morning stiffness. Flurbiprofen was better tolerated (p less than 0.01).
 
Article
The mechanism of action of various types of drugs for treating inflammation and arthritis is reviewed. Three classes of agents, the steroidal, the acidic non-steroidal and the basic therapy drugs, are discussed. The first two types of drugs act rapidly on the symptoms of inflammation, interfering at various points in the inflammatory response. The non-steroidal agents are especially linked to a mechanism involving, at least in part, the prostaglandins. Piroxicam, a potent, structurally unique member of the non-steroidal class, is discussed in some detail. The basic therapy drugs act slowly, generally exhibit more severe side effects and probably affect some immunological aspects of rheumatoid arthritis. The precise mechanisms of action of this latter class of structurally diverse drugs is generally poorly understood at this time.
 
Article
One hundred and thirty-one male and female outpatients, aged 18-70 yr, with acute pain in the ankle joint caused by a post-traumatic sprain, entered a multicentre, randomised, double-blind, parallel-group, study. The patients were assigned to a 40 mg flurbiprofen patch (n = 65) or a non-medicated (but otherwise identical) control (n = 66), 12-hourly over 7 days, and were assessed at entry and after 3 and 7 days treatment. On day 7, spontaneous pain (the prime efficacy parameter), as evaluated by the patient on a visual analogue scale in the physician's office, showed significant improvement in the 40 mg flurbiprofen patch group compared to control (change from baseline) (p = 0.039), a result corroborated by the evaluation of the periarticular oedema: a reduction of 77.4% was observed in the 40 mg flurbiprofen patch group, compared with 63.8% in the control group (p = 0.025). The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance. Two mild and local adverse events were reported by two flurbiprofen patch patients, but neither patients discontinued the treatment prematurely. Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated. Compliance was excellent in both groups. The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains.
 
Article
Superoxide anion (0(-2)), hydrogen peroxide (H2O2) and hydroxyl radical (OH.) are products of the biological reduction of 0(2). They are very reactive and poorly tolerated within living systems and enzymes that catalytically scavenge these products have been evolved as defense mechanisms. These include superoxide dismutases (SOD), catalase and peroxidases. Large amounts of O-2 are produced by different enzymatic and non enzymatic biological processes. Large amounts of activated oxygens are produced by phagocytosing cells such as macrophages and polymorphonuclear cells. This production is associated with the bactericidal actions of these cells but it also largely contributes to exacerbate and sustain the inflammation where these cells congregate. The arachidonic acid pathway triggered by the inflammatory stimuli is also a source for these oxidizing radicals. The production of activated oxygens has been associated with the normal aging process but also with various toxic reactions (e.g. the toxicity of the herbicide paraquat, of the ionizing radiations, of certain antibiotics such as streptonigrin, etc. . . .). O-2 induces the depolymerization of hyaluronic acid which lends viscosity and lubricating properties to synovial fluids. SOD possess antiinflammatory properties and a bovine SOD, orgotein, has now been largely investigated by intramuscular and intraarticular injections in the treatment of rheumatic diseases. Various antiinflammatory compounds (e.g. the salicylates) are able either to inhibit the production of these oxygen radicals or to scavenge them which seems of importance for their antiinflammatory properties. Singlet oxygen, another activated oxygen, might also play a role in the inflammatory process.
 
Article
Forty patients with osteoarthritis of the hips or knees entered a double-blind crossover study, in which 50 mg t.i.d. indomethacin was compared to a single daily dose of 600 mg benoxaprofen. Patients were randomly allocated to either indomethacin or benoxaprofen for four weeks and then transferred to the alternate drug without a washout period. Thirty-one patients completed the entire trial period. Both indomethacin and benoxaprofen led to a statistically significant improvement (alpha less than or equal to 0.05) of the subjective (measured by a pain score) and the objective joint status (range of motion evaluation) as compared to the pretreatment status. With regard to efficacy, there was no statistically significant difference between the two drugs. Benoxaprofen proved to be the better tolerated compound, causing four dropouts. Six patients were excluded from the indomethacin treatment due to severe gastrointestinal side effects. There also was a higher number of other side effects with indomethacin, but none severe enough to discontinue treatment. With the doses used, both compounds proved to be similar in efficacy in osteoarthritic conditions although benoxaprofen was the better tolerated drug.
 
Article
A 17 year old Caucasian youth with intractable Crohn's disease developed a severe, acute polyarthropathy during a second course of levamisole therapy. Rapid resolution of systemic symptoms occurred on stopping the drug but full joint recovery was not achieved until five months had elapsed. The relationship of levamisole to Crohn's disease and the underlying mechanisms of the polyarthropathy are discussed.
 
Article
181 patients suffering from acute locomotor affections linked with sports activities were included in a multi-center study. The indications most frequently seen were sprains and tendinitis. 92 patients received piroxicam in a daily dosage of 4 capsules (40 mg) during the first two days, then 20 mg during the following days. 89 patients received a daily dose of indomethacin in a daily dose of 6 capsules (150 mg) for the first two days, and then 100 mg daily thereafter. Treatment lasted from 5 to seven days. Efficacy was judged to be very good or good in 89% of the patients treated with piroxicam against 76% of those treated with indomethacin, a statistically significant difference. Tolerance was also judged better with piroxicam. 4 patients suffered side effects with piroxicam, of which one stopped treatment after the second administration due to allergic reaction. 18 patients treated with indomethacin suffered from side effects, of which 5 stopped the treatment. In total, the use of piroxicam seems particularly interesting in sports medicine in comparison with indomethacin.
 
Article
Analgesics continue to be the mainstay of therapy in osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role, particularly where there is a significant inflammatory component to the osteoarthritis. Piroxicam-beta-cyclodextrin (PBC) is a new formulation in which piroxicam has been complexed with beta-cyclodextrin, a cyclic oligosaccharide. This results in an increase in the rate of absorption of the active compound and, consequently, in an earlier onset of analgesic action. PBC, like piroxicam, is administered once daily. PBC has been used in the treatment of osteoarthritis. In comparison with piroxicam, PBC showed a more rapid analgesic-anti-inflammatory action after the first administration in patients with active osteoarthritis. Subsequent evaluations at the second, fifth and last day of treatment demonstrated a comparable efficacy of the two drugs. The efficacy and tolerability of PBC was compared with other NSAIDs given intramuscularly, such as diclofenac and ketoprofen. The three compounds provided marked pain relief within thirty minutes and this increased progressively until the third to fourth hour. The efficacy of oral PBC was comparable to that of intramuscular diclofenac or ketoprofen. In comparison with metamisole PBC achieved a more rapid and sustained reduction in pain intensity during the first twelve hours of treatment. This rapid and marked reduction in pain intensity with PBC was also observed in patients with low-back pain when compared with etodolac. In view of its efficacy, tolerability and rapid onset of action, piroxicam-beta-cyclodextrin appears to be an useful analgesic and a prominent progress in the treatment of acute rheumatic pain.
 
Article
Tenoxicam is a new thienothiazine derivative belonging to the oxicam chemical group, which has been shown to possess potent anti-inflammatory activity in animal models of induced inflammation. Tenoxicam specifically inhibits the synthesis of prostaglandins and platelet aggregation. Like most NSAIDs, tenoxicam is a weak acid whose solubility depends on the pH of the medium. Given orally, tenoxicam is rapidly absorbed and its bioavailability is >90%. As a consequence of its great affinity for plasma protein binding, its half-life is on average 72 hours (range 42-98 hours) allowing once-daily administration. This study compared different dosing regimens of tenoxicam. A total of 27 patients (22 males, 5 females; average age 61.2 ± 7.6 years) were studied using two experimental designs: (i) a double-blind study comparing a daily dose of 20 mg tenoxicam versus 40 mg given during six days and (ii) a comparative open study of a single dose of 60 mg against two doses separated by a 24-hour interval. The patients were selected on the basis of verification of one or more of the following criteria: presence of sodium urate crystals in the synovial fluid (during the present or previous attacks); presence of trophi; attack affecting the big toe; hyperuricaemia > 7.5 mg%. As evaluation criteria of the activity of tenoxicam, the following variables were taken into account: spontaneous pain, pain on touch and on movement, inflammation, heat and local redness, as well as the perimeter of the affected joint. The results showed that daily doses of 20 and 40 mg given during six days were equally effective, with statistically significant differences with the 40 mg dose in the speed of improvement of pain on touch, local redness and inflammation (p < 0.05). In all 10 patients who received two doses of 60 mg, excellent results were obtained whilst with a single dose of 60 mg an initial improvement was observed followed by exacerbation of some of the clinical parameters on the fourth day of control. The results in this group were good in six patients and moderate in one. Tenoxicam was very well tolerated and only one patient who received 20 mg daily referred with slight epigastralgia. Systemic tolerance was good.
 
Article
General Practitioners from the United Kingdom produced data on 1,282 patients with acute soft tissue injury treated with either piroxicam (Feldene) or matching placebo for a period of up to two weeks. The dosage of piroxicam was 40 mg for the first 2 days and 20 mg daily thereafter. Clinical assessment included pain, swelling, limitation of active and passive movement and overall assessment of efficacy and toleration. Piroxicam was significantly better than placebo in improving patient signs and symptoms, and in its overall efficacy (P less than 0.001); 87% of piroxicam treated patients had excellent or good responses, compared to 53% of placebo treated patients. On analysis of four of the most commonly occurring diagnoses (injuries of ankle, knee, shoulder, back) patients with moderate or severe pain showed a significant improvement on treatment with piroxicam. Physicians' overall assessment of toleration showed no evidence of differences between treatments. Over 90% of patients in both treatment groups had good or excellent toleration. Withdrawals due to side effects were 3% and 2.5% respectively for piroxicam and placebo treated patients.
 
Article
In two multicentre double-blind, parallel studies, piroxicam was found to be as well tolerated and significantly more effective than placebo in relieving moderate and severe pain, swelling, and limitation of movement resulting from acute musculoskeletal injuries. The efficacy and toleration of piroxicam were then compared with those of indomethacin and naproxen in two international multicentre double-blind trials involving 1,004 patients suffering from acute sprains or tendinitis resulting from sports injuries; a common study protocol was used in all centres. In all treatment groups, spontaneous pain, pain on movement, joint swelling, and tenderness were reduced significantly as early as three days after the start of treatment, and overall assessment of efficacy was excellent or good in more than 80% of patients. The study results indicated that the efficacy of all drugs was comparable, but analysis of side effects reports showed that piroxicam was significantly (p less than 0.005) better tolerated by the patients.
 
Article
The authors carried out an open noncomparative study to evaluate the anti-inflammatory therapeutic activity of piroxicam in 40 adult patients suffering from acute gout. The patients ranged in age from 28 to 68 years (the average age was 51.6 years) overall, 21 men and 19 women participated in the trial. All of the patients had their disease for more than one year and they were receiving treatment with Benziodarone, 100 mg per day when the drug was discontinued from clinical use in Brazil. All of these patients subsequently experienced aggravation of their disease and had an acute attack of gout. Each patient was given piroxicam, 40 mg, in a single dose on the first day and two divided doses of 20 mg for the following five days. The affected joints were: elbow, knee, ankle and hallux. Severity of pain at rest, severity of pain on movement, tenderness, swelling, redness, heat and restriction of movement were evaluated. By the sixth day of the trial, good or total remission was observed in all patients. Overall evaluation of efficacy showed excellent and good results in 81.6% of the patients. Tolerability was excellent and good in 92.5%. All adverse reactions that occurred during the use of piroxicam therapy were noted. Five patients showed mild side effects, such as pyrosis, nausea and headache, and two patients had severe side effects (skin rash, gastric disturbance) that necessitated withdrawal from therapy. Finally, statistical analysis demonstrates that piroxicam is highly efficacious in the treatment of acute gout.
 
Article
Percutaneously administered niflumic acid gel (Niflugel R, Laboratories UPSA, Rueil Malmaison, France) was compared to placebo in a double blind, placebo controlled, multicentre study in the treatment of acute upper and lower limb tendinitis. Fifty nine subjects were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied three times daily for 7 days. Clinical evaluations were carried out on inclusion and after seven days of treatment. The variables measured were pain felt by the patient and the investigators' and patients' overall evaluation of the treatments' efficacy. The patients also kept a daily record of pain scores. Any adverse events that occurred were noted. The results showed that niflumic acid gel was significantly better than placebo in improving patient signs as regards overall efficacy ratings. Global evaluation of efficacy rated by the investigator showed that 25/29 patients (86.2%) were healed or improved in the niflumic acid gel group compared with 11/27 patients (40.7%) on placebo, p = < 0.01. The overall assessment of tolerance showed no difference between groups. Only two minor adverse effects were reported in patients treated with niflumic acid gel, and they did not require patients to stop treatment. The study findings indicate that treatment with topical niflumic acid gel is effective in the treatment of tendinitis and results in improved clinical signs at the end of 7 days.
 
Article
Cultured human endothelial cells exposed to interleukin-1 (IL-1) exhibited increased adhesiveness for human polymorphonuclear leukocytes (PMNs). This phenomenon was dose-dependent, maximal increased adhesion being observed at 0.25 U/ml IL-1. ECs required a minimum exposure time of 30 min. with IL-1 followed by at least 1-2 hours incubation for expression of increased adhesiveness. Incubation for shorter periods of time did not induce significant changes in EC-PMN adhesion compared with cultures having received no IL-1. No change in adhesion was observed when IL-1 was co-incubated with ECs and PMNs. Similar results were observed using lipopolysaccharide (LPS) as stimulus. It is concluded that increased adhesion of PMNs to vascular endothelium is mediated by the direct interaction of endogenous (IL-1) and exogenous (LPS) substances with ECs, the expression of which requires a latent period of 1-2 hours and is protein synthesis-dependent. The implications of these novel findings in pathological disease states are discussed.
 
Article
The ability of benoxaprofen to suppress bone damage associated with adjuvant-induced arthritis in rats was studied radiographically over a 49-day period. Benoxaprofen was administered orally at a daily dose of 30 mg/kg. Treated and control groups of rats were examined at seven-day intervals from 14 through 49 days. Benoxaprofen showed significant suppression of bone damage at all time intervals. Benoxaprofen was compared in a radiographic bone study with other nonsteroidal anti-inflammatory agents. Benoxaprofen at doses of 10-40 mg/kg/day orally, administered from days 15 to 39 of the disease, was more effective in suppressing bone damage exhibiting toxic effects than other agents. This modification of the experimental disease process by benoxaprofen may be due in part to its reported ability to suppress monocyte migration into inflammatory sites.
 
Article
Nabumetone, a novel nonsteroidal anti-inflammatory drug, has aroused considerable interest due to mounting evidence suggesting a diminished potential for causing gastrointestinal mucosal irritancy. In the present study, rats were administered equally effective oral suspensions of either nabumetone (79mg/kg), ibuprofen (88mg/kg), diclofenac (11.5mg/kg), or a control suspension (n = 8 or 9 per group) daily for one month and subsequently assessed for various indices of anti-inflammatory activity, gastrointestinal irritancy, and prostaglandin inhibitory activity. Daily doses were five times the ID25 for carrageenan-induced paw inflammation as obtained in previous studies. At the end of the administration period, nabumetone maintained effective antiinflammatory activity, but was devoid of gastrointestinal irritancy. In contrast, ibuprofen and diclofenac were associated with marked and significant gastrointestinal mucosal damage. The findings of the present study support published preclinical and clinical studies establishing nabumetone as an effective anti-inflammatory agent with a favourable gastrointestinal safety profile.
 
Article
Seventy-nine patients with arthrosis (40) or rheumatoid arthritis (39) were included in an open, non-comparative multicentric study. All the patients were treated by rectal route with a suppository form of tenoxicam (20 mg/day) during 6 weeks (in the first 3 days the dose was increased to 40 mg). The drug was administered once daily at evening. Clinical evaluation was performed before treatment and thereafter every 2 weeks. In the patients with arthrosis the parameters evaluated for efficacy were: pain on movement, pain at rest, tenderness, spontaneous pain, pain after 1 day of normal activity, flexion, functional status, and time to walk 10 metres. For patients with rheumatoid arthritis the parameters were: articular index, duration of morning stiffness, functional status, spontaneous pain and pain when moving. Efficacy was considered excellent or good in 22 patients with rheumatoid arthritis and moderate or poor in 17. In the group of patients with arthrosis the results were excellent or good in 28 and moderate or poor in 12. Side effects occurred in five cases.
 
Article
Male and female patients suffering from rheumatoid arthritis with normal renal function or with renal impairment were treated in hospital with 300 mg of fenbufen 8 hourly for fourteen days. Concentrations of fenbufen and its principal metabolites were measured by high pressure liquid chromatography on days 0, 7, 10 and 14 and also four days after discontinuation of the drug. Renal impairment does not produce cumulation of either fenbufen or its major metabolites in the plasma. The metabolite profile of the drug was similar to that observed in patients with normal renal function.
 
Article
Twenty eight patients who received corticosteroids for rheumatoid arthritis for at least five years were studied. Short synacthen tests were carried out in twenty two of these patients and twelve showed a subnormal response. This response was unrelated to initial or present dose, duration of treatment or activity of disease. Ten patients accepted our offer of steroid reduction. Reduction proved difficult because of patient resistance although the only index of inflammation to worsen was the articular index. We postulate that patient resistance to withdrawal may be due to some factor other than the loss of the anti-inflammatory effect of corticosteroids.
 
Article
This study analyses the results of 8 randomized, controlled clinical trials and one open study carried out with droxicam (a new NSAID, pro-drug of piroxicam), comparing the adverse events and gastrointestinal tolerance of this compound against those of the control drugs used in these trials. The frequency of adverse events was lower in the droxicam treated patients. Adverse events concerning the gastrointestinal area were also lower. No differences were found in the distribution of adverse events by age of sex among the drugs compared. The pattern of side effects found was that expected in all non-steroidal anti-inflammatory agents. These results seem to sustain the hypothesis of a better tolerance of droxicam than that of piroxicam, indomethacin or diclofenac, especially in the gastrointestinal area.
 
Article
To determine the effects of nabumetone, compared with tiaprofenic acid and etodolac, on anti-inflammatory efficacy and gastrointestinal irritancy in the rat when dosed orally for one month at a high anti-inflammatory dose. Carrageenan paw edema was used as a model of inflammation. Gastrointestinal mucosal integrity was assessed by concurrently measuring ulcer formation. mucosal and tissue prostanoid production and plasma haptoglobin. Haemoglobin, present in the cecal contents, was used as a measure of blood loss. Nabumetone, tiaprofenic acid and etodolac inhibited inflammation. Etodolac induced marked gastrointestinal damage and blood loss whereas tiaprofenic acid caused only gastric damage. Nabumetone was found not to alter mucosal integrity. Nabumetone proved to be an effective anti-inflammatory agent that was devoid of gastrointestinal irritancy.
 
Article
Long term studies with nabumetone have confirmed that it is an effective NSAID, comparable to other agents including aspirin and naproxen. Large scale post-marketing studies have shown high response rates and good tolerance.
 
Article
Indoprofen, a new non-steroidal antirheumatic agent, was tested in a controlled, double-blind, cross-over study versus indomethacin and placebo, in 30 patients with rheumatoid arthritis. The study consisted of three fourteen-day treatment periods. At the end of the trial 14 patients expressed a preference for the indoprofen therapy (200 mg q.i.d.), 10 patients for indomethacin (25 mg q.i.d.) and 5 patients decided in favour of the placebo. Judging from the patients' assessment of spontaneous pain, a complete analgesic effect was observed in 44% of the patients under indoprofen, in 26% under indomethacin and in 13% under placebo. Indoprofen showed good efficacy on all the other parameters measured (Ritchie's index, morning stiffness, number of painful and swollen joints, and grip strength) and good clinical and biological safety.
 
Article
Indoprofen is an isoindoline derivative of phenylpropionic acid. At doses of 1-3 mg/kg it inhibited acute and subchronic experimental inflammation. Its strong analgesic activity lacks any specific CNS effect. The drug's pharmacological activity is directly related to inhibition of prostaglandin biosynthesis at the cyclo-oxygenase step. In carrageenin-induced oedema indoprofen and prednisolone had a synergistic anti-inflammatory effect, and indoprofen and acetylsalicylic acid showed an additive effect. Acute and chronic toxicity of indoprofen was determined in the mouse, rat, dog and monkey. Target organ for indoprofen toxicity is the gastrointestinal tract (ulcerogenic effect). In vitro and in vivo studies of mutagenicity did not show any mutagenic activity. No embryotoxic or teratogenic effect was noted in reproduction toxicity studies in rats, rabbits and monkeys.
 
Top-cited authors
Kerstin Menander
  • PEREGRINE PHARMACEUTICALS, INC.
Mario Carrabba
  • Ospedale Luigi Sacco
Michele Angelini
Che Che
  • Sabaragamuwa University of Sri Lanka
Kay Brune
  • Friedrich-Alexander-University of Erlangen-Nürnberg