CS-600, a new anti-inflammatory agent

II. Pharmacological efficacy and ulcerogenic effect of CS-600 and its active metabolite

Abstract

Anti-inflammatory, analgesic and ulcerogenic activities of CS-600 and its active metabolite were investigated in rats. Anti-carrageenin edema activity of CS-600 (ID₅₀: 1.2 mg/kg) was as potent as that of the active metabolite (ID₅₀: 1.3 mg/kg) . Analgesic effect of CS-600 (ID₅₀: 0.76 mg/kg) on scald pain was also equipotent to that of the metabolite (ID₅₀: 1.1 mg/kg) . However, gastrointestinal irritancy of CS-600 (UD₅₀: 16.1 mg/kg for the stomach and 11.5 mg/kg for the intestine) was lower than that of the active metabolite (UD₅₀: 3.2 mg/kg for the stomach and 3.1 mg/kg for the intestine) . When [¹⁴C] CS-600 was injected into a ligated jejunum in rats, most radioactivity was found as the unchanged CS-600 in the portal blood. These findings indicate that CS-600 is absorbed from the intestine in the less irritating form and that it is converted rapidly to the active metabolite which shows the potent pharmacological efficacy.