The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [¹⁴C] cetagliptin in healthy volunteers

Abstract

1. The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50μCi [¹⁴C] cetagliptin.

2. The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [¹⁴C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336 h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.

3. Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulphate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and faeces at low levels, except that metabolite M640B was not detected in faeces. All metabolites were observed with <10% of parent compound systemic exposure after oral administration.

Keywords:

• Cetagliptin
• metabolism
• excretion
• metabolite
• healthy subjects

Acknowledgments

The authors acknowledge the First Affiliated Hospital of Soochow University (Suzhou, China) for conducting this study. The authors acknowledge Value Pharmaceutical Services Co., Ltd for the radiometric analysis of the human plasma, faeces and urine.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was sponsored by CGeneTech (Suzhou, China) Co., Ltd. The work is supported by China national science and technology major project for significant new drug development funding project [2018ZX09301007-001].