European journal of rheumatology and inflammation最新文献

Altogether 1,912 patients have been enrolled in studies of nabumetone in the United States. They were all patients with osteoarthritis or rheumatoid arthritis. After completing participation within randomised studies patients were entered into an open study which continued for up to five years. These cases provide longterm efficacy and safety data for the use of nabumetone. About 25% of patients were withdrawn because of lack of efficacy; most of these withdrawals were in the first year of therapy. There was a similar picture with side-effects. About 12% of patients were withdrawn, mostly in the first year. Many patients continued to take nabumetone for five years without adverse effects and with continuing efficacy. The numbers of patients in whom nabumetone was stopped due to lack of efficacy or an adverse reaction was similar in those aged over 65 years and in patients aged less than 65 years. These results show that nabumetone is a safe and effective anti-inflammatory drug in long term clinical use.

Attitudes to prescribing anti-inflammatory drugs have changed considerably over the last 25 years and there is now a recognition of the need to balance effectiveness with reduced risks of serious adverse reactions. Such serious side-effects often involve the upper gastrointestinal tract, and there are differences between anti-inflammatory drugs in the frequency with which they cause significant problems at this site. Anti-inflammatory drugs with a lesser propensity to cause gastrointestinal reactions may have an advantage. Several risk factors may be important for upper gastrointestinal side-effects including sex, age, history of dyspepsia, other diseases and the type of arthritis. Results from post-marketing surveillance studies of nabumetone in the United Kingdom and the Federal Republic of Germany showed that although patients with a previous history of dyspepsia were more likely to stop the drug due to an adverse reaction, the majority continued without any problem. Interestingly, patients with rheumatoid arthritis were more likely to stop therapy due to side-effects, though it was not clear if this was due to their disease or to multi-morbidity. Strategies are needed when prescribing anti-inflammatory drugs which take into account the type of patient, their disease, and the best drug. In many instances this could be nabumetone.

A single oral dose pharmacokinetic study in a group of 10 elderly healthy volunteers was performed to evaluate the pharmacokinetic profile and the potential effect of age on the absorption, distribution and elimination of droxicam. After complete medical screening, and informed written consent, one dose (20mg) of droxicam was administered to all volunteers, under medical supervision. A complete pharmacokinetic profile of the obtained blood plasma levels was evaluated over 120 hours. All volunteers completed the study and in none did droxicam cause intolerance or side effects. The results showed that droxicam absorption, distribution and elimination did not differ substantially from reference studies done with young healthy volunteers. The peak mean plasma concentration was at 10 hours 1.38 +/- 0.29 microgram/ml, declining slowly, reaching 0.24 +/- 0.20 microgram/ml at 120 hours, with a half life of 50.23 +/- 17.19 hours and an elimination rate constant of 0.015 +/- 0.005 microgram/ml.h-1. In comparison to the healthy, young volunteers, the variation was minimal. It can be concluded from this study that age causes minimal variations in the absorption and distribution of droxicam.

Nabumetone is an effective anti-inflammatory drug in models of inflammation and in man, comparable in potency to other compounds of this type. It differs from other compounds in several important respects. The parent molecule is non-acidic and virtually inactive but is transformed to an active metabolite (6MNA) by the liver. 6MNA is not excreted in bile and cannot therefore, by reflux from the small intestine, reach the stomach. Many other compounds can reach the stomach in this way even when given by routes other than oral, for example by suppository. Prostaglandin production by the stomach, a protective mechanism, is not markedly affected by 6MNA whereas it is suppressed by other NSAIDs. These studies suggest a favourable therapeutic ratio for nabumetone.

A new in vitro model for studying cartilage breakdown has been utilised in this work. Polymorphonuclear neutrophils (PMNs) with phorbol myristate acetate (PMA) were layered onto 2 microns cryostat sections of bovine nasal cartilage. After incubation, the sections were fixed, stained, and the amount of glycosaminoglycan (GAG) contents measured by microdensitometry. PMNs caused GAG loss from sections and this was greatly enhanced when the PMNs were activated by PMA. Various pharmacological agents were then added to the system, namely acetyl salicylic acid, indomethacin, ibuprofen, piroxicam, dexamethasone, D-penicillamine, chloroquine and BN50548. The drugs tested had no direct effect on cartilage matrix, nor did they affect GAG loss from sections treated with non-stimulated PMNs. However, BN50548, a novel protease inhibitor, afforded a dose response protection of cartilage section from GAG loss by PMA stimulated PMNs. This model may prove to be of value in screening novel antiproteases with chondroprotective activity.

Droxicam is a new non-steroid anti-inflammatory drug that is a pro-drug of piroxicam. The pharmacokinetics of droxicam, both as a single 10mg dose and as a multidose regimen of 10 and 20mg/day for 20 consecutive days, have been studied in healthy volunteers. Since transformation into piroxicam takes place in the gastrointestinal tract, unchanged droxicam was not detected in plasma. After a single 10mg dose the value of Tmax was higher than that reported for piroxicam (10mg). This effect is a consequence of the process of transformation of droxicam into piroxicam. The remaining pharmacokinetical parameters studied were similar to those reported in other studies on piroxicam (10mg). After multiple oral administration at a dose of 10 and 20mg/day, absorption kinetics of droxicam were delayed with respect to those of piroxicam. The other pharmacokinetical parameters studied showed no statistically significant differences between droxicam and piroxicam. Absorption and elimination of droxicam are independent of the administered dose and the bioavailability of droxicam and piroxicam was equal. The influence of gastric emptying on droxicam pharmacokinetics and bioavailability has been investigated in healthy volunteers. Gastric emptying was experimentally modified by use of propantheline and metoclopramide. Following modification of gastric emptying, only Tmax underwent significant increase (P < 0.05). Absorption rate of droxicam was modified but elimination and bioavailability did not suffer modification in conditions of altered gastric emptying.

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.

This randomized, controlled and double-blind clinical trial compares the efficacy of droxicam (20mg/day) with that of indomethacin (75mg/day) in 40 RA patients (11 male, 29 female) aged (+/- SD) 53 +/- 12.5 years. After a 7-day single-blind run-in placebo period, patients were divided into two groups and treated for 9 weeks. Assessments were done at baseline and at the end of the 1st, 2nd, 4th, 6th and 9th weeks. Both drugs improved significantly the articular pain, the duration of morning stiffness, the articular index, the functional status and the degree of fatigue. Patient's and doctor's opinions were in accordance with the above-mentioned results. The effect of both drugs was more noticeable in the first 2 weeks of treatment. Droxicam was found to be statistically more active than indomethacin in alleviating morning stiffness and improving the functional status. The improvement of the variables induced by droxicam increased progressively throughout the study whereas that induced by indomethacin remained unchanged after the 2nd or 4th week of treatment. One patient treated with indomethacin withdrew from the study due to staggering and dizziness and several patients reported dyspepsia. Droxicam seems to be as effective as indomethacin (75mg/day) in the symptomatic relief of RA patients. The possibility of the use of droxicam for the relief of morning stiffness is of particular interest.

Many problems make it difficult to estimate the exact risk of peptic ulceration and its complications, perforation and bleeding, in patients receiving NSAIDs. Nevertheless the association of these events and treatment is now beyond dispute. Deaths are a particular problem in the elderly since mortality from peptic ulcer disease rises steeply after age 60. Risk factors identified with hospitalisation for gastrointestinal problems in patients receiving NSAIDs include age, previous gastrointestinal symptoms, corticosteroid use and disability. The risk of death is highest in elderly females and is substantial.