Definition

A first-generation sulfonylurea with hypoglycemic activity. Tolbutamide binds to and blocks adenosine triphosphate (ATP)-sensitive potassium channels on the beta cell membrane of the pancreatic islet tissues. This leads to potassium efflux, which results in depolarization, calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis. In addition, tolbutamide may increase the number and affinity of cell surface insulin receptors, thereby enhancing the peripheral response to insulin. Tolbutamide is a CYP2C9 substrate.