Background:

Sulfaphenazole is a strong and competitive inhibitor of CYP2C9 [1]. CYP2C9 is a major cytochrome P450 enzyme involved in the metabolic clearance of various therapeutic agents, such as oral anticoagulants, nonsteroidal anti-inflammatories, and oral hypoglycemics. Disruption of CYP2C9 activity results in many adverse drug reactions [2].

In vitro: In yeast expressed human cytochromes P450 of the 1A, 3A, and 2C subfamilies, sulfaphenazole acts as a strong and competitive inhibitor of CYP 2C9 with the Ki value of 0.3 ± 0.1 μM. The Ki values of sulfaphenazole for CYP 2C8 and 2C18 were 63 and 29 μM, respectively. Sulfaphenazole failed to inhibit CYP 1A1, 1A2, 3A4, and 2C19 [1].

In vivo: In diabetic male mice (db/db strain), daily intraperitoneal injections of either the CYP 2C inhibitor sulfaphenazole (5.13 mg/kg) for 8 weeks, sulfaphenazole restored endothelium-mediated relaxation in db/db mice. Sulfaphenazole reduced oxidative stress, increased NO bioavailability and restored endothelial function in db/db mice [3].

参考文献:
[1] Mancy A, Dijols S, Poli S, et al.  Interaction of sulfaphenazole derivatives with human liver cytochromes P450 2C: molecular origin of the specific inhibitory effects of sulfaphenazole on CYP 2C9 and consequences for the substrate binding site topology of CYP 2C9[J]. Biochemistry, 1996, 35(50): 16205-16212.
[2] Rettie A E, Jones J P.  Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics[J]. Annu. Rev. Pharmacol. Toxicol., 2005, 45: 477-494.
[3] Elmi S, Sallam N A, Rahman M M, et al.  Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice[J]. Vascular pharmacology, 2008, 48(1): 1-8.