[Pharmacologic studies on Ro 12-0068, a new non-steroidal anti-inflammatory drug (author's transl)]

Abstract

The pharmacological profile of Ro 12-0068 as a new anti-inflammatory agent has been established in 9 different animal models and was compared with the profiles of 10 reference drugs. In adjuvant arthritis, scald-related edema and bradykinin-induced capillary permeability tests, the inhibitory potency of Ro 12-0068 was greater than findings in the case of diclofenac sodium which was the most potent agent available, while Ro 12-0068 exerted a stronger inhibitory effect on granuloma formation than did indomethacin. Anti-inflammatory potency of Ro 12-0068 in other models was equivalent to that of piroxicam. Ro 12-0068 was categorized as a potent anti-inflammatory agent and was grouped with diclofenac sodium, indomethacin and piroxicam, as compared to rather weak agents such as naproxen, carprofen, phenylbutazone, flufenamic, mefenamic, and acetylsalicylic acids. In fasting rats, ulcerogenicity of Ro 12-0068 in the gastric glandular and duodenal portions was weaker than that of indomethacin, appeared to be less than that of piroxicam and was equivalent to that of diclofenac sodium. Induction of fecal occult bleeding in dogs was markedly greater in case of indomethacin and piroxicam than with Ro 12-0068, within few days after oral treatment. Ro 12-0068 and piroxicam had much the same inhibitory effect on prostaglandin synthesis of inflammatory tissues and exudates from gastro-intestinal tissues. Nevertheless, therapeutic indices of Ro 12-0068 in rats were larger than those of piroxicam, in all models, and those of indomethacin in most cases. These results strongly suggest that Ro 12-0068 is a potent anti-inflammatory agent and that the occurrences of related gastro-intestinal disturbances are fewer.