RT Journal Article
SR Electronic
T1 In vivo metabolism of isoxicam in rats, dogs, and monkeys.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 662
OP 668
VO 17
IS 6
A1 T F Woolf
A1 A Black
A1 J L Hicks
A1 H Lee
A1 C C Huang
A1 T Chang
YR 1989
UL http://dmd.aspetjournals.org/content/17/6/662.abstract
AB Isoxicam is a long half-life nonsteroidal anti-inflammatory agent which undergoes extensive metabolism prior to elimination in animals and man. The major route of isoxicam transformation is hydroxylation of the methylisoxazole functionality to form hydroxymethylisoxicam, and cleavage of its benzothiazine moiety to give an oxoacetic acid metabolite. The metabolic pathway for scission of the benzothiazine moiety to the oxoacetic acid metabolite and to other potential metabolites is not known. To gain additional information on the metabolic fate of isoxicam, 14C-isoxicam labeled on the N-methyl group was administered to rats, dogs, and monkeys with urine and feces collected for metabolic profiling and identification. Identified as new metabolites of isoxicam were an open-ring sulfonamide, N-methylsaccharin, and saccharin. The formation of these metabolites suggests that isoxicam undergoes direct oxidative scission of its benzothiazine ring at carbon atom 3 to generate the observed open-ring sulfonamide, N-methylsaccharin, and oxoacetic acid metabolites.