Abstract

Upon administration of the nonsteroidal anti-inflammatory agent furobufen to mice, rats, dogs, and man, 2-dibenzofuranacetic acid (DBFA) was rapidly formed and was the major circulating metabolite. There was a species difference in the rate of DBFA formation; the serum elimination half-lives (t1/2) of furobufen and DBFA were 25 min and 6 hr in rats, 35 min and 15 hr in dogs, and 3 hr and approximately 20 hr in man, respectively. After oral and intravenous administration of 14C-furobufen to rats and dogs, virtually all of the serum radioactivity was due to furobufen and DBFA. Serum levels of DBFA in rats, dogs, and man increased in proportion to the oral dose. The t1/2 of furobufen and DBFA in man did not appear to be altered by chronic treatment and were the same in both sexes. Furobufen and DBFA were strongly bound to human serum protein (greater than 99%). A method was elaborated to measure serum furobufen and DBFA spectrophotofluorometrically in the presence of salicylates. Serum levels of furobufen and DBFA were lower in rats treated with aspirin; the effect was dependent upon the dose of aspirin. At the doses used, aspirin did not affect serum furobufen and DBFA in dogs and man.