Multi-centre double-blind study to define the most favourable dose of nimesulide in terms of efficacy/safety ratio in the treatment of osteoarthritis.

A parallel group study for one month of 392 patients was undertaken to define the optimal dose of nimesulide for the treatment of painful osteoarthritis (OA). By the final visit, the mean values for pain intensity for the nimesulide groups (50 mg, 100 mg and 200 mg bd) were similar and significantly lower than the mean for the placebo group. The onset of analgesia was rapid and continued throughout the 12-hour period after drug intake, a significant analgesic effect was demonstrated with nimesulide 100 mg and 200 mg within 1.5 hours. The patients' and the physicians' overall judgements of the drug efficacy demonstrated significant differences between the treatment groups with the most successful outcomes occurring with nimesulide 100 mg and 200 mg. Nimesulide 50 mg and 100 mg were generally well-tolerated but at the highest dose level, nimesulide 200 mg, the incidence of adverse events was greater although not significantly. Results of this study demonstrate nimesulide 100 mg twice daily to be the optimal dose for the treatment of OA.

Treatment of tendinitis and bursitis: a comparison of nimesulide and naproxen sodium in a double-blind parallel trial.

The clinical efficacy and the tolerability of nimesulide (100 mg bid) and naproxen sodium (550 mg bid) in the treatment of tendinitis and bursitis were evaluated in a multicentre double-blind study over a 14-day period. Two hundred and five patients were included in the study. Patients randomised to one of two parallel treatment groups. They were clinically examined at days 1, 7 and 14. Blood analysis was performed at day 1 and at the end of the treatment. The main efficacy criterion was the diminution of pain during active mobilisation measured using a visual analogue scale. The improvement of the scores was obvious and similar between the two groups. The secondary efficacy criteria (pain during motion against resistance, functional impairment and global assessment of efficacy) confirmed these favourable results and did not evidence any statistical difference between the two groups. The side effects observed were mainly gastrointestinal. Their frequency and intensity were slightly higher in the naproxen sodium group but without any statistically significant difference (28 complaints in 16 patients in the nimesulide group and 33 complaints in 22 patients in the naproxen group). There was no statistical difference between the two treated groups regarding the general clinical examination and the biological follow-up.

Nimesulide granules for the treatment of acute inflammation of the ear, nose or throat.

The efficacy of nimesulide (100mg twice daily) was compared with that of naproxen (500mg twice daily) in 53 adult patients with nonbacterial acute inflammation of the ear, nose or throat in a double-blind phase III clinical investigation. Both drugs were administered orally after meals for a mean duration of 8.7 days. In this setting, nimesulide was associated with relief of pain and inflammatory signs (exudation and swelling). Indeed, treatment with nimesulide led to clinical improvement superior to that obtained with naproxen in terms of both rapidity of action and improvement of the symptoms at the end of therapy. Nimesulide therapy was also very well tolerated and no patient reported an adverse event. In contrast, 2 naproxen-treated patients reported episodic gastralgia of moderate intensity.

Controlled clinical investigation of acute analgesic activity of nimesulide in pain after oral surgery.

A double-blind study was conducted to determine the dose-effect relationship of nimesulide and to compare the acute analgesic activity of this agent with that of placebo and niflumic acid. Patients undergoing extraction of an impacted third molar were randomised into 4 groups (nimesulide 100mg; nimesulide 200mg; niflumic acid 250mg and placebo). They were instructed to take their allocated treatment after the onset of pain, and to record the pain severity and relief during the following 6 hours. 134 patients were evaluated. There were significant differences between groups for each time of observation/efficacy parameter (Kruskal-Wallis test). Pairwise comparison (Duncan's test) showed that all 3 active medications were significantly different from the placebo. No substantial differences were found between any of the active treatments. Analogous results were obtained when the amount of rescue drug used (paracetamol) was compared. More positive judgements were reported by patients treated with an active compound than by those taking placebo.

A double-blind comparison of nimesulide and mefenamic acid in the treatment of acute upper respiratory tract infections in children.

The efficacy and safety of nimesulide suspension were evaluated in comparison with mefenamic acid in a double-blind multicentre study that recruited 100 children with acute respiratory tract infections. On entry, each child was randomly allocated to receive either nimesulide 5 mg/kg/day or mefenamic acid 5 mg/kg divided into 2 or 3 daily doses as an oral suspension, for a period of 3 to 10 days. Body temperature returned to normal on the third day for most of the nimesulide-treated patients, but only on the fifth day for the mefenamic acid group. There was a significant difference (p < 0.01) between the antipyretic activity of nimesulide and that of mefenamic acid. Furthermore, treatment with nimesulide was associated with clinically significant improvement in all inflammatory signs and symptoms observed (rhinorrhoea, nasal obstruction, pharyngeal redness, swelling of lymph nodes and cough). Adverse effects considered possibly related to treatment were recorded for 3 patients treated with nimesulide and 1 with mefenamic acid.

Analysis of uterine contractility after administration of the non-steroidal anti-inflammatory drug nimesulide.

To study the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on uterine contractility in different parts of the uterus and on the direction and velocity of propagation of the activity, intra-uterine pressure (IUP) was measured simultaneously in 10 dysmenorrheic and 5 eumenorrheic patients with two microtransducer catheters at two locations (30 mm apart) before and after taking nimesulide, a newly developed NSAID. The uterus developed higher pressure cycles in the fundus than in the isthmus, in both eumenorrheic and dysmenorrheic conditions. Nimesulide did not affect either the active pressure (AP) or the direction and velocity of propagation of the activity, though it alleviated pain significantly. In dysmenorrheic patients, resting pressure (RP) is at a high level only in the fundus. The velocity of propagation ranged from 12 to 19 mm/s. The mathematical probability of procervical activity (1.0 if all procervical; 0.0 if all profundal), and thus the transport, was 0.59 in eumenorrheic and 0.68 in dysmenorrheic patients, the average for the whole series being 0.65. The luminal content (menstrual blood) moves in the cervical direction much more slowly than would be expected on the basis of simple calculations of velocity (velocity vector) of propagation.

Pilot study of the antipyretic and analgesic activity of nimesulide paediatric suppositories.

The object of this study was the preliminary evaluation, in paediatric patients, of the analgesic and antipyretic effect of nimesulide given rectally. Nimesulide was studied in comparison with paracetamol, according to a double-blind technique. Forty-eight hospitalized children with fever or pain, between 1 and 8 years old, were included. The drugs were administered with a flexible posology (1 to 4 suppositories/day with an interval between administrations of at least 6 h). Monitoring of symptom intensity was scheduled in the 6 hours after each administration. At the end of the therapy the physician expressed a global judgement on the drug. Both treatments resulted in a significant decrease in body temperature at the 1 h observation. From the second hour onward, a more rapid tendency to temperature normalization was observed with nimesulide than with paracetamol. Repeated measurements with ANOVA did not show significant differences between treatments but the physicians' overall judgements were significantly more favourable to the nimesulide than to the paracetamol antipyretic activity. Good analgesic activity, favouring a rapid decrease in the painful symptomatology, was observed in both groups. No differences were found in the analgesic activity of the treatments, although in this case the clinical evidence was more favourable to paracetamol. Both drugs were very well tolerated.

Distribution of oral nimesulide in female genital tissues.

Nimesulide is a non-steroidal anti-inflammatory agent which has proved to be effective in reducing menstrual discomfort in dysmenorrhoeaic women. To determine the concentrations of this drug in the uterus (fundus, cervix), oviduct, and ovaries and to correlate these findings with plasma concentrations, a single oral dose of 100 mg nimesulide was administered 1 to 6 h before surgery to 12 women undergoing hysterectomy and salpingo-oophorectomy, mainly for fibroids. Tissue samples were taken, concentration of nimesulide measured by HPLC, and findings compared with plasma concentrations. One patient not undergoing treatment served as control. Nimesulide concentration in the tissues studied was highest 3 h after administration, as expected from the drug's pharmacokinetic profile. The highest tissue/plasma ratio (0.5) was also found at that time. Average tissue concentrations at 1, 2, 3, and 6 h after drug intake ranged from 0.3 to 1.8 micrograms g-1, and plasma concentrations from 2.6 to 4.1 micrograms ml-1. Nimesulide was evenly distributed in the tissues studied.

Antipyretic effects of nimesulide in paediatric practice: a double-blind study.

A double-blind, multi-centre study was carried out in 42 hospitalized children, aged 6 months to 8 years, suffering from acute respiratory tract infections with fever, to investigate the antipyretic activity of nimesulide. On entry, patients were allocated at random to receive either nimesulide oral suspension, 5 mg/kg/day divided into 3 daily doses, for 5 days or placebo. Both groups were treated simultaneously with antibiotics: children under 5 years of age received 100 mg amoxycillin/kg/day, those over 5 years received 40 to 50 mg erythromycin/kg/day. Measurements of rectal temperature before and during the 6 hours after the first dose of nimesulide showed a significant mean decrease from a baseline value of 38.89 +/- 0.74 degrees C to 37.28 +/- 0.76 degrees C at 6 hours. In the placebo group, no significant changes were observed between baseline (38.82 +/- 0.67 degrees C) and the 6-hour value (38.28 +/- 1 degree C). Morning temperatures remained within the normal range on the following days. Nimesulide was well tolerated. The results indicate that nimesulide has a prompt antipyretic effect which may well be clinically helpful before the correct antibiotic therapy is effectively established.

Pharmacokinetics and therapeutic study with nimesulide suppositories in children with post-operative pain and inflammation.

The pharmacokinetic pattern of 100 mg nimesulide administered rectally at different times prior to undergoing minor surgery was studied in 45 children. Absorption of nimesulide was relatively fast, a peak plasma concentration of 75 mg/l being reached 3 h after administration, and the elimination half-life was 3.15 h. The efficacy and tolerability of the nimesulide suppositories were assessed in a randomized, double-blind, dipyrone-controlled study of 50 children suffering from moderate to severe post-operative pain, the drugs being administered one to three times daily as required; 26 patients received nimesulide and 24 dipyrone. A consistent reduction in pain was recorded during nimesulide therapy given for a mean period of 2.5 days, with a mean consumption of 3.5 suppositories. Similar results were obtained in dipyrone-treated patients. The efficacy of both drugs was judged by the physicians to be good or very good in 70% of cases and there were no statistically significant differences between the two treatment groups in the dosage required or the pain relief. Tolerability of both drugs was excellent, with only one patient in each treatment group complaining of nausea.

Antipyretic activity of nimesulide suppositories: double blind versus diclofenac and placebo.

The acute antipyretic activity of nimesulide 200 mg suppositories was tested in a double-blind trial using diclofenac 100 mg suppositories as active reference drug and placebo as blank reference. Eighty-one patients (52 males and 29 females) aged between 18 and 90 years (mean 65 +/- 16.4), with fever of various etiology entered the study. Body temperature, heart rate and blood pressure were recorded before the drug administration and than after 30, 60, 90, 120, 240 and 360 minutes. Nimesulide proved to be as effective as diclofenac in normalizing body temperature and fever related objective signs (heart rate and arterial pressure), significantly shortening fever duration with respect to placebo. The tolerability of both treatments was in general good: 3 cases of nimesulide group (10%) and 4 cases of diclofenac group (17%) complained of slight and transitory side effects. No side effects were complained in the placebo group.