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Xenobiotica
the fate of foreign compounds in biological systems
Volume 44, 2014 - Issue 6
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Clinical Pharmacokinetics and Metabolism

Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans

, , , , , & show all
Pages 522-530 | Received 25 Sep 2013, Accepted 11 Nov 2013, Published online: 04 Dec 2013
 

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) [14C]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.

Acknowledgements

The authors thank Korea RadioChemicals Center, for the synthesis of radiolabeled compound. They also thank K. Dummer and K. Sweeney for the assessment of mass balance recovery, metabolite profiling and identification.

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