The effect of
THS-201, a new intra-articular
steroid, on
inflammations was examined using acute, subacute and chronic experimental models, and the antiinflammatory action of
THS-201 was compared with those of reference
steroids such as
triamcinolone acetonide (TA),
methylprednisolone acetate (MPA),
hydrocortisone acetate (HA) and halopredone (HP). Reference
steroids, which were given s.c. or locally, dose-dependently inhibited
carrageenin-induced foot-pad
edema,
sodium carboxymethyl cellulose-induced leukocyte migration, cotton pellet
granuloma and
carrageenin granuloma pouch in rats. Although the inhibitory effects of reference
steroids on such
inflammations were unrelated to their administration routes, the inhibitory potency decreased in the following order: TA greater than MPA greater than HA = HP.
THS-201 even at a dose of 100 mg/kg had no inhibitory effects on such
inflammations when given s.c. By contrast,
THS-201 given locally had anti-inflammatory actions: the inhibitory potency of
THS-201 in chronic models was higher than that of TA, but was lower in the acute models than that of HA. In
antigen-induced
arthritis in rabbits, the inhibition of swelling of inflamed joints by
intra-articular injection of
THS-201 (2 mg/joint) persisted more than 30 days, suggesting that the elimination of
THS-201 from the injected site was very slow. In contrast to the finding of reference
steroids,
THS-201 showed no systemic adverse reactions in all experiments. The results, which are in agreement with the findings of labeled
THS-201 into arthritic joints, indicate that
THS-201 can strongly inhibit recurrence of
inflammation as compared with reference
steroids tested.(ABSTRACT TRUNCATED AT 250 WORDS)