AUTHOR=Park Jin-Woo , Kim Kyoung-Ah , Kim Jong-Min , Park In-Hwan , Park Ji-Young 

TITLE=Influence of FMO3 and CYP3A4 Polymorphisms on the Pharmacokinetics of Teneligliptin in Humans

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.736317

DOI=10.3389/fphar.2021.736317

ISSN=1663-9812

ABSTRACT=<p>Teneligliptin, a dipeptidyl peptidase-4 inhibitor, is used to treat type 2 diabetes mellitus. FMO3 and CYP3A4 metabolize teneligliptin into teneligliptin sulfoxide. This study examined the effects of <italic>FMO3</italic> (rs909530, rs1800822, rs2266780, and rs2266782) and <italic>CYP3A4</italic> (rs2242480) polymorphisms on teneligliptin pharmacokinetics at a steady state among 23 healthy participants administered 20 mg teneligliptin daily for 6 days. Subjects with <italic>FMO3</italic> rs909530, rs2266780, and rs2266782 polymorphisms exhibited a significant gene dosage-dependent increase in maximum steady-state plasma drug concentration (C<sub>max,ss</sub>) and area under the drug concentration vs time curve (AUC) (<italic>p</italic>&lt;0.05). However, the C<sub>max</sub> values significantly decreased but the AUC values did not significantly vary in subjects with <italic>CYP3A4</italic> polymorphism (rs2242480). These results suggest that <italic>FMO3</italic> and <italic>CYP3A4</italic> polymorphisms affect teneligliptin pharmacokinetics in humans. The findings of this study provide a scientific basis for the inter-individual variation in teneligliptin disposition.</p>