Absorption, metabolism, and excretion of [¹⁴C]evogliptin tartrate in male rats and dogs

ABSTRACT

The objective of this study was to determine the absorption, excretion, and metabolism of a novel, oral antihyperglycemic drug, evogliptin, in male rats and dogs. Plasma, urine, feces, and expired air samples were collected after a single oral dose administration of [¹⁴C]evogliptin, samples were analyzed by measuring overall radioactivity levels using high-performance liquid chromatography (HPLC), and radioactivity levels were measured by utilizing LC-tandem mass spectrometry (LC-MS/MS). The total amounts of radioactivity excreted in urine, feces, and expired air up to 168 h after administration of [¹⁴C]evogliptin tartrate to rats (30 mg evogliptin/kg) and dogs (10 mg evogliptin/kg) were 96.7% and 96.8% of initial doses administered, respectively. The extent of urinary and fecal excretion in the rat up to 168 h constituted 29.7% and 66.5% of the given dose, respectively; and in dog was 43.3% and 53.5%, respectively. A total of 23 possible metabolites were detected with radiochromatograms of plasma, urinary, and fecal samples, but only the structures of 12 metabolites were identified via LC-MS/MS analysis. Evogliptin was the major component. Regarding the total radiochromatographic peak areas, peaks 9 (evogliptin acid) and 11 (hydroxyevogliptin) were the major metabolites in rats, and peaks 8 [4(S)-hydroxyevogliptin glucuronide], 15 [4(S)-hydroxyevogliptin], and 17 [4(R)-hydroxyevogliptin] were the predominant metabolites in dogs. Data demonstrated that evogliptin was the major component excreted in urine and feces of rats and dogs, but the metabolite profiles varied between species.

Acknowledgments

We thank Atsushi Takao and Shinobu Gunji, ADME &Tox. Research Institute, Sekisui Medical Co., Ltd for the technical assistance