ADDRESS FOR CORRESPONDENCE:
SeungHwan Lee, MD, PhD
Department of Clinical Pharmacology and Therapeutics, Seoul National
University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu,
Seoul, 03080, Republic of Korea
Tel: +82-2-2072-2343; Fax: +82-2-742-9252
E-mail address:
leejh413@snu.ac.kr
RUNNING TITLE: Pharmacokinetic/Pharmacodynamic interaction
between evogliptin and glimepiride
DATA SHARING: Please contact the corresponding author for
questions concerning data sharing.
ABSTRACT
Aims: Evogliptin, a
dipeptidyl peptidase-4 (DPP-4) inhibitor and glimepiride, a
sulfonylurea, have been used to treat type 2 diabetes mellitus. This
study aimed at evaluating the pharmacokinetic (PK) and pharmacodynamic
(PD) interactions between evogliptin and glimepiride.
Methods: A randomized, open-label, 3-period, 3-treatment,
2-sequence crossover study was conducted in healthy male subjects.
During each period, subjects received multiple doses of evogliptin 5 mg
alone (EVO), glimepiride 4 mg alone (GLI), or co-administration of the
two (EVO+GLI). Serial blood and urine samples for PK and PD analyses
were collected 168 and 24 hours post-dosing, respectively.
Results: Thirty-four subjects completed the study.
Co-administration of evogliptin and glimepiride did not alter their
plasma and urine PK profiles. For evogliptin, the geometric mean ratio
(GMR) (90% confidence intervals) for the maximum plasma concentrations
at steady-state (Cmax,ss) and the area under the curve
during dosing interval at steady-state (AUCτ,ss) of
EVO+GLI to E were 1.02 (0.98 – 1.06) and 0.97 (0.95 – 1.00),
respectively. For glimepiride, the corresponding values of EVO+GLI to
GLI were 1.08 (1.01 – 1.17) and 1.08 (1.02 – 1.14), respectively. All
values were within the regulatory bioequivalence criteria of 0.80 –
1.25. Administration of EVO+GLI decreased the glucose excursion compared
to evogliptin and glimepiride monotherapy, respectively.
Conclusion: Evogliptin and glimepiride had no PK interactions
when co-administered, while combination therapy showed an additive
glucose lowering effect compared to those of evogliptin or glimepiride
monotherapy.