European journal of rheumatology and inflammation最新文献

The ability of articular cartilage to withstand repeated mechanical loading with relatively little wear over a lifetime results from the properties of the extracellular matrix (ECM) and the optimal function of the chondrocytes which are responsible for the synthesis and presumably maintenance of this ECM. The properties of the ECM are accounted for by the relationship of the major aggregating, polyanionic, negatively charged proteoglycans with their potent viscoelastic properties to the network of collagens and several noncollagenous proteins. The major collagen (type II) interacts with type IX collagen in a highly specific manner. Type IX collagen has a chondroitin sulfate side chain and can also bind to the aggregating proteoglycans through a basic amino terminal domain. In inflammation, injury and probably repeated wear, function of the chondrocytes is disturbed, mediated by the action of potent cytokines, which results in release of degradative enzymes and alterations in the pattern of synthesis of the ECM. Identification of the critical cytokines and the sequence of events that result from their action should provide the basis for rational prophylaxis and therapy of disorders such as osteoarthritis and rheumatoid arthritis. Articular cartilage has unique mechanical properties which permit repeated mechanical loading with relatively little wear over a lifetime. These properties result from the special character of the extracellular matrix (ECM) and optimal functioning of the component cells (chondrocytes) which are responsible for the synthesis and presumably, maintenance of this matrix. Articular chondrocytes survive and perform these critical functions in an anaerobic environment remote from the vasculature and must derive their nutrition from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

The chronicity of the inflammatory process requires persistent tissue concentrations of non-steroidal anti-inflammatory drugs (NSAIDs), best achieved by using a drug with a long half-life as a once-daily regimen. The oxicams proved to be one of the most promising classes of NSAIDs. They have a similar molecular structure, though substitution of the benzothiazine ring by a thienothiazine system gives tenoxicam a more hydrophilic character. Tenoxicam is thus characterised by lower penetration into tissues requiring more lipophilic properties, e.g. the CNS and skin and, consequently, a lower incidence of adverse reactions at these target organs. Poor diffusion into hepatic cells--as a result of a small free fraction, tight binding to proteins and hydrophilic character--explains its low hepatic extraction ratio and--as a consequence--a long half-life. Compared to indomethacin and diclofenac, the oxicams have a moderate inhibitory activity on the synthesis and release of prostaglandins; tenoxicam is half as active as piroxicam, reflecting the correspondent difference in their steady-state plasma concentrations.

The pharmacokinetics and bioavailability of two piroxicam formulations, 20-mg capsules for oral administration and 20-mg solution for intramuscular injection, were studied in 18 healthy male volunteers. A 40-mg dose was administered on the morning of the first two days, and a 20-mg dose on five subsequent days. Four weeks after the first dose was administered, the regimen was repeated, according to a crossover design. Plasma levels of piroxicam were measured with high performance liquid chromatography (HPLC) using ultraviolet detection at 340 nm. Results of ANOVA, Westlake, and Wilcoxon tests show that the two preparations are bioequivalent. The intramuscular solution, however, produces comparatively higher piroxicam plasma concentrations up to 45 minutes after the first 40-mg dose, up to 30 minutes after the second 40-mg injection, and up to 15 minutes after the 20-mg maintenance doses. The terminal half-lives were found to be 58.1 +/- 2.3 hours after intramuscular administration and 60.2 +/- 2.5 hours after oral dosing.

Some new aspects of the pharmacokinetics of piroxicam have recently become of interest because of the wide use of this compound. Recent studies have provided data on several questions: Are the disposition kinetics of piroxicam different from those of nonsteroidal anti-inflammatory drugs (NSAIDs) with a short half-life, and are the differences in transsynovial distribution relevant to anti-inflammatory activity and significant in the clinical use of these drugs in acute and chronic rheumatic conditions? Are there important differences in the disposition and elimination of piroxicam from patient to patient and in special subgroups such as elderly patients? Is the variation in the half-life of a drug within a given population significant, especially with regard to the rate of metabolic degradation, enterohepatic recirculation, and tubular reabsorption?

There is little consistency in drug treatment of children with juvenile rheumatoid arthritis, in part because there are few controlled studies of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in this disease. To determine the safety and efficacy of piroxicam in children with juvenile rheumatoid arthritis, 26 patients ranging in age from three to 25 years were randomly assigned to treatment with piroxicam or naproxen. The number of painful and swollen joints decreased significantly (p less than 0.05) in the piroxicam group. The overall assessment of the investigators was that 67% of the patients in the piroxicam group showed clinical improvement, in contrast to 38% of the naproxen-treated patients. Side effects in the piroxicam group were mild and transient, and no patient was removed from the study because of side effects. The recurrence of a cutaneous rash necessitated the removal of one naproxen-treated patient from the study. Although the results should be interpreted with caution because of the small sample size, piroxicam appears to be more effective and better tolerated than naproxen in this study.

The prescription-event monitoring procedure developed at the University of Southampton was used to evaluate five different non-steroidal anti-inflammatory drugs (NSAIDs), including piroxicam, in approximately 55,000 patients. The overall incidence of side effects was what would be expected. The risks of gastrointestinal haemorrhage and peptic ulceration were spread uniformly across the five drugs under study. No real difference was seen in the incidence of these conditions when patients discontinued the medication or switched to another NSAID. Overall, serious side effects were extremely rare. One provocative finding was the possibility that drugs of this class may exert a cardioprotective effect. There appeared to be a deficit of cases of myocardial infarction while the patients were taking an NSAID. Responsibility for the efficacy and safety of all drugs resides with many people and organizations: the manufacturers, national health departments, licensing departments, and physicians. The press, which has contributed to many unwarranted panics concerning drug safety, also must refrain from using power without responsibility.