Category: pharmacological
Aliases: Orinase
First-generation sulfonylurea hypoglycemic for type 2 diabetes. Closes pancreatic β-cell K_ATP channels (SUR1/Kir6.2) → depolarization → voltage-gated Ca²⁺ entry → insulin secretion. Almost entirely metabolized by CYP2C9 to hydroxymethyl- and carboxytolbutamide — making tolbutamide the canonical CYP2C9 probe substrate in classical DDI studies. Now rarely used clinically (displaced by 2nd/3rd-gen sulfonylureas + GLP-1 agonists + SGLT2 inhibitors) but retained in the registry as the workhorse CYP2C9 probe. PK (Orinase label, 500 mg PO single): Cmax 39-52 mg/L, Tmax 3-4 h, t½ 4.5-6.5 h, F well-absorbed (~80% est), protein binding ~95% (small Vd ~14 L follows). Food does not alter absorption. CYP2C9 substrate — canonical probe for CYP2C9 phenotyping + DDI assessment (fluconazole / sulfaphenazole / aprepitant DDIs documented).
PO: 5.5h