Sudoxicam

Sudoxicam is a reversible and orally active COX antagonist and a non-steroidal anti-inflammatory drug (NSAID) from the enol-carboxamide class. Sudoxicam has potent anti-inflammatory, anti-edema and antipyretic activity[1][2][3].

Sudoxicam demonstrates NADPH-dependent covalent binding to human liver microsomes. With addition of glutathione (GSH) in microsomal incubations, about half of the covalent incorporation of Sudoxicam is blocked by addition of GSH[1].Metabolite identification studies on [14C]-Sudoxicam in NADPH-supplemented human liver microsomes indicated that the primary route of metabolism involved a P450-mediated thiazole ring scission to the corresponding acylthiourea metabolite (S3), a well-established pro-toxin[1].In vitro, Sudoxicam underwent the oxidative thiazole-open biotransformation, resulting in the formation of an acylthiourea and the subsequent hydroxylated metabolite[3].

Sudoxicam (1-10 mg/kg; oral administration; daily; for 7 days; rats) treatment effective reduces plasma inflammation units, reduces the swelling of inflamed hind-paws and restores toward normal the daily gain in body weight[2].In the intact rat, Sudoxicam significantly inhibited edema formation at doses as low as 0.1 mg/kg, p.o[2].Sudoxicam inhibits the erythema caused by ultraviolet irradiation in the guinea pig. Sudoxicam (3.3 mg/kg, i.p.) is capable of counteracting the pyrexia induced by the intraperitoneal injection of typhoid/paratyphoid vaccine in rats, maintaining body temperature about that of uninjected control rats[2]. The plasma half-life of Sudoxicam ranged between 8 hours (monkey), 13 hours (rat), and 60 hours (dog)[2].

[1]. Obach RS, et al. In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti-inflammatory agents sudoxicam and meloxicam: insights into the hepatotoxicity of sudoxicam. Chem Res Toxicol. 2008 Sep;21(9):1890-9.
[2]. Wiseman EH, et al. Anti-inflammatory and pharmacokinetic properties of sudoxicam N-(2-thiazolyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide. Biochem Pharmacol. 1972 Sep 1;21(17):2323-34.
[3]. Zhi-Yi Zhang. Sudoxicam. Handbook of Metabolic Pathways of Xenobiotics. September 2014.