Metabolism, excretion, and pharmacokinetics of [¹⁴C]mirogabalin, a novel α₂δ ligand, in healthy volunteers following oral administration

Abstract

1. The metabolism, excretion, and pharmacokinetics of mirogabalin were investigated following a single oral administration of [¹⁴C]mirogabalin at 30 mg/5.55 MBq to six healthy male subjects.

2. The mean recovery values of radioactivity in urine and faeces were 96.85 and 1.21%, respectively. The main component of radioactivity in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), mirogabalin N-glucuronide, and glucuronide of oxidized A204-4455 were detected as minor components in the specimens. Renal clearance of mirogabalin was higher than the glomerular filtration rate of the human kidneys, indicating renal secretion is involved in the clearance.

3. In vitro studies revealed that UDP-glucuronosyltransferase produced two metabolites: A204-4455, formed via mirogabalin acylglucuronide, and a ring-opened form of mirogabalin N-glucuronide.

4. Mirogabalin was absorbed almost completely, and was eliminated via urine. A part of the orally administered dose of mirogabalin was metabolized through glucuronidation at the amine and carboxylic acid moiety, which represents the primary metabolic pathway.

Keywords:

• Mirogabalin
• urinary excretion
• active secretion
• glucuronidation
• lactam
• human

Acknowledgements

The authors acknowledge Ling He (Daiichi Sankyo Pharma Development) for bioanalytical support. The authors expresses thanks to Hiroko Koda (Daiichi Sankyo Co., Ltd.) for structure elucidation of metabolites and Hideyuki Shiozawa to discuss ring size and its cyclization. The authors also acknowledge Takeo Kasagami (LSI Medience Corporation at the time of the study) for conducting quantitative metabolite profiling of the human specimen.

Disclosure statement

NY, MU, YU and MT are full-time employees of the Sponsor, Daiichi Sankyo. JM-H, HK, KB, VW, and VV were a full-time employee of Daiichi Sankyo at the time of the clinical study.

Additional information

Funding

This work was not supported by any funding agency.