| Abstract: | The anti-inflammatory activity and mode of action of topically applied pranoprofen-gel were investigated in comparison with indomethacin-gel in experimental animals. Applied topically, 0.3 approximately 3% pranoprofen-gel inhibited carrageenin-induced paw edema, fracture-induced paw edema, carrageenin-induced increase in vascular permeability and adjuvant arthritis in rats and ultraviolet ray-induced erythema in guinea pigs dose-dependently, with a potency slightly greater than that of indomethacin-gel. In addition, pranoprofen-gel inhibited dose-dependently the formation of granuloma caused by a cotton pellet implantation, without affecting the weight of the thymus or adrenals and without inducing gastrointestinal lesions. Moreover, applied topically to carrageenin-treated rats, pranoprofen-gel inhibited dose-dependently, and more potently than indomethacin-gel, the production of a prostaglandin E2 (PGE2)-like substance in both the exudate of the carrageenin air pouch and the inflamed synovial membrane. Both drugs inhibited the potentiation of bradykinin-induced vascular permeability in rabbit skin by arachidonic acid, but not by PGE2. Pranoprofen was only one third as potent as indomethacin in inhibiting the production of PGE2 from the phagocytosing of killed bacteria by rat peritoneal leucocytes in vitro. These results show that pranoprofen-gel, applied topically, permeates well from the skin to the deep inflammatory site, relieving potently and long lastingly the inflammation by inhibiting PG production. As a topical anti-inflammatory agent, pranoprofen-gel is at least as effective as indomethacin-gel, so it may have good clinical use. |
