Sign Out
Pharmacology: Pharmacodynamics: Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4) enzyme resulting in prolonged active incretin levels. Incretin hormones (e.g., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production.
Pharmacokinetics: Absorption: Sitagliptin was rapidly absorbed, with peak plasma concentrations occurring 1 to 4 hours post-dose. The absolute bioavailability of sitagliptin is approximately 87%.
Distribution: The mean volume of distribution at steady state is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma protein is low (38%).
Metabolism: Not extensively metabolized; minor metabolism via CYP3A4 and CYP2C8 to metabolites (inactive).
Excretion: Approximately 87% were eliminated in urine (79% as unchanged drug, 16% as metabolites) and 13% were eliminated in feces, respectively. Half-life elimination is 12.4 hours.
