[Inhibitory action of non-steroidal anti-flammatory drugs on prostaglandin synthesis and release (author's transl)]

Abstract

Inhibitory action of non-steroidal anti-inflammatory drugs (NSAID)on the synthesis and release of prostaglandin (PG) was studied both in vivo and in vitro. In the experiment with PG synthetase from beef seminal vesicle, the potency of NSAID on the inhibitory action of PGE synthesis was: flurbiprofen greater than 4-(p-chlorophenyl)-2-phenyl-5-thiazoleacetic acid (CH-800) greater than indomethacin greater than diclofenac-NA greater than aspirin. Inflamed synovial tissue, as induced 6 hours after carrageenin injection into the knee joint cavity of rats was used to examine the inhibitory action of NSAID on PGE release from the tissue. Both in vivo and in vitro, CH-800 was the most potent and flurbiprofen and indomethacin were next potent of the five drugs. Effects of NSAID on the excretion of PGE and PG main urinary metabolite (PGMUM) in rat urine were determined. The excretion of urinary PGE was significantly decreased by administration of NSAID. Flurbiprofen and CH-800 had the most potent inhibitory action on the excretion of PGEMUM, but the urinary excretion of PGFMUM was not significantly inhibited by NSAID. Thus, the inhibitory effects of NSAID associated with PG synthesis were generally in proportion to the effect of the drugs with PG synthetase, however, there were differences regarding PG synthesis in inflamed tissue and the urinary excretion of PG metabolites.