Distribution of oxametacine and its anti-inflammatory metabolites in inflamed tissues of rats.

The anti-inflammatory drug oxametacine (1-p-chlorobenzoyl-5-methoxy-2-methyl-3-indolylacetohydroxamic acid) is extensively metabolized both in laboratory animals and in man. In rats, dosed orally with 5 mg/kg [14C]-oxametacine, there is a 2.2-2.7 fold increase in radioactivity in the inflamed tissues, in the hind-paws of animals with adjuvant arthritis and in the granulomas of cotton-pellet implanted rats. The total tissue radioactivity (following two-fold extraction with methanol; recoveries being 95 +/- 3%) was distributed into the following metabolites: 34-7% oxametacine, 26-37% indomethacin, 16-46% demethylindomethacinamide, and 26-10% indomethacinamide over 2-8 h following drug administration.