IMPROVED ORAL BIOAVAILABILITY OF SALICYLAMIDE IN RABBITS BY A 1,3-BENZOXAZINE-2,4-DIONE PRODRUG

The oral bioavailability of 1,3-benzoxazine-2,4-dione was investigated in rabbits and compared with that of salicylamide. The benzoxazinedione was shown to be hydrolyzed to salicylamide both in vitro and in vivo. The oral bioavailability of salicylamide was increased 2.5-fold following administration as 1,3-benzoxazinedione comapared to oral dosing of an equimolar amount of salicylamide per se. This increased bioavailability of salicylamide was ascribed to a diminished first-pass metabolism achieved by protecting the vulnerable phenolic group in the form of a benzoxazinedione ring structure.