Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. (June 2014)

• Record Type: Journal Article
• Authors: Kim, Namtae; Patrick, Lorna; Mair, Stuart; Stevens, Lloyd; Ford, Gill; Birks, Vicky; Lee, Sung-Hack
• Is Part Of: Xenobiotica. Volume 44:Number 6(2014:Jun.)
• Page Start: 522
• Page End: 530
• Publication Date: 2014-06
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2013.865856
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>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) [¹⁴C]gemigliptin to healthy male subjects, absorption, metabolism and excretion were investigated.</p> <p>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.</p> <p>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.</p> </abstract>