title: Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans.
abstract: 1. Gemigliptin (formerly known as LC15-0444) is a newly developed dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes. Following oral administration of 50 mg (5.4 MBq) [(14)C]gemigliptin to healthy male subjects, absorption, metabolism and excretion were investigated. 2. A total of 90.5% of administered dose was recovered over 192 hr postdose, with 63.4% from urine and 27.1% from feces. Based on urinary recovery of radioactivity, a minimum 63.4% absorption from gastrointestinal tract could be confirmed. 3. Twenty-three metabolites were identified in plasma, urine and feces. In plasma, gemigliptin was the most abundant component accounting for 67.2% ∼ 100% of plasma radioactivity. LC15-0636, a hydroxylated metabolite of gemigliptin, was the only human metabolite with systemic exposure more than 10% of total drug-related exposure. Unchanged gemigliptin accounted for 44.8% ∼ 67.2% of urinary radioactivity and 27.7% ∼ 51.8% of fecal radioactivity. The elimination of gemigliptin was balanced between metabolism and excretion through urine and feces. CYP3A4 was identified as the dominant CYP isozyme converting gemigliptin to LC15-0636 in recombinant CYP/FMO enzymes.
authors.affiliation: LG Life Sciences, Drug Metabolism and Pharmacokinetics , Daejeon , Republic of Korea .
authors.forename: Namtae
authors.initials: N
authors.lastname: Kim
authors.forename: Lorna
authors.initials: L
authors.lastname: Patrick
authors.forename: Stuart
authors.initials: S
authors.lastname: Mair
authors.forename: Lloyd
authors.initials: L
authors.lastname: Stevens
authors.forename: Gill
authors.initials: G
authors.lastname: Ford
authors.forename: Vicky
authors.initials: V
authors.lastname: Birks
authors.forename: Sung-Hack
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D065569:Gastrointestinal Absorption; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D010881:Piperidones / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011485:Protein Binding; D011743:Pyrimidines / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D054873:Dipeptidyl-Peptidase IV Inhibitors; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines