Absorption, metabolism and excretion of [14C]omarigliptin, a once-weekly DPP-4 inhibitor, in humans

Abstract1. Omarigliptin (MARIZEV®) is a once-weekly DPP-4 inhibitor approved in Japan for the treatment of type 2 diabetes. The objective of this study was to investigate the absorption, metabolism and excretion of omarigliptin in humans.2. Six healthy subjects received a single oral dose of 25 mg (2.1 μCi) [14 C]omarigliptin. Blood, plasma, urine and fecal samples were collected at various intervals for up to 20 days post-dose. Radioactivity levels in excreta and plasma/blood samples were determined by accelerator mass spectrometry (AMS).3. [14 C]Omarigliptin was rapidly absorbed, with peak plasma concentrations observed at 0.5–2 h post-dose. The majority of the radioactivity was recovered in urine (∼74.4% of the dose), with less recovered in feces (∼3.4%), suggesting the compound was well absorbed.4. Omarigliptin was the major component in urine (∼89% of the urinary radioactivity), indicating renal excretion of the unchanged drug as the primary clearance mechanism. Omarigliptin accounted for almost all ...