A comparison of the effects of tixocortol pivalate (JO 1016), hydrocortisone acetate and beclomethasone dipropionate on collagen synthesis and degradation.

The effects of a corticosteroid substitute pregn-4-ene-3,20-dione-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol, JO 1016, Pivalone), hydrocortisone acetate and beclomethasone dipropionate on collagen metabolism in mouse calvariae were compared by histological and biochemical determination of collagen content, and by radio-assays of collagenase and collagenase inhibitor. Hydroxyproline assay revealed dose-related increases in collagen content/wet wt. tissue. These were greatest in explants treated with beclomethasone dipropionate, tixocortol pivalate being effective only at much higher concentrations than the other 2 drugs. Hydrocortisone acetate and beclomethasone dipropionate stimulated collagenase production at the lowest levels tested whereas tixocortol pivalate was only slightly stimulatory at the highest treatment level. These results suggest that in clinical use tixocortol pivalate would be much less likely than hydrocortisone acetate or beclomethasone dipropionate to cause degenerative changes in connective tissue.