A panel of non-steroidal anti-inflammatory drugs commonly used for therapeutic purposes was assessed for their effects on the respiratory burst of isolated human polymorphonuclear neutrophils. Cells were stimulated with opsonised yeast and the production of reactive oxygen species was measured by amplified chemiluminescence with luminol and lucigenin which are two luminogenic agents measuring different cellular events. A special attention was devoted to the establishment of dose–effect curves and calculation of ED 50 . Some of the drugs tested (acemetacine, diclofenac, flufenamic acid and niflumic acid) were able to decrease both luminol and lucigenin chemiluminescence in a dose-dependent manner reflecting an inhibitory effect on the respiratory burst. The most potent derivative was flufenamic acid (ED 50 8 and 78 μ M, respectively, with luminol and lucigenin), followed by diclofenac (21 and 98 μ M), niflumic acid (97 and 227 μ M) and acemetacine (585 and 427 μ M). In contrast, several other drugs (flurbiprofen, ibuprofen, ketoprofen, piroxicam) stimulated both luminol and lucigenin chemiluminescence, suggesting a pro-oxidant activity. Acetylsalicylic acid (up to 1250 μ M) was a modest inhibitor (maximum 25% inhibition) showing no dose-dependant effect and tolmetin (up to 125 μ M) had no significant effect in both systems. The results were in agreement using both luminogenic agents, except for indomethacin, naproxen and tenoxicam which showed different kinds of effects. The unspecific and complex nature of the measurement systems used did not allow to give a complete mechanistic interpretation of the results, but the comparison with literature data gave some pertinent explanations for both anti- and pro-oxidant effects.
The range in amounts of the dosage units of Flupirtin and the amounts of the antiphlogistic set forth above are exchangeable for each other. Thus for example in the combination Flupirtin-Diclofenac the dosage unit contains 10-300 mg Flupirtin and 3-50 mg Diclofenac or 10-300 mg Flupirtin and 8-20 mg Diclofenac or 25-150 mg Flupirtin and 3-50 mg Diclofenac or 25 to 150 mg Flupirtin and 5-30 mg Diclofenac. It is obvious these ranges can be so correlated in relation to each other that in each case the largest general range of Flupirtin is related to the largest general range of the antiphlogistic (for example a combination of 10-300 mg Flupirtin and 3-50 mg Diclofenac), the preferred range of Flupirtin to the preferred range of each antiphlogistic and the "especial range" of Flupirtin to the "especial range" of each antiphlogistic.
The effect of piroxicam (1 x 20 mg daily), diclofenac (2 x 50 mg daily) and indomethacin (3 x 25 mg daily) on renal function was compared in a double-blind cross-over study of 33 patients with various rheumatologic diseases. Individuals with preexisting renal impairment were excluded. In 16 patients piroxicam was compared with diclofenac. In another group of 17 patients piroxicam was compared with indomethacin. Each drug was given for 28 days. The mean inhibition of renal prostaglandin E2 by the three drugs was comparable. There was no significant alteration of the renal function parameters in any of the drugs. These results confirm that nonsteroidal antiinflammatory drugs with short (diclofenac, indomethacin) but also with long half life (piroxicam) do not decrease renal function in individuals without renal impairment.