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Effects of clarithromycin on the pharmacokinetics of evogliptin in healthy volunteers
Author(s) -
Oh E. S.,
Choi C.,
Kim C. O.,
Kim K. H.,
Kim Y. N.,
Kim S. J.,
Park M. S.
Publication year - 2017
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12604
Subject(s) - pharmacology , cmax , pharmacokinetics , clarithromycin , chemistry , medicine , helicobacter pylori
Summary What is known and objective Evogliptin ( DA ‐1229), a novel dipeptidyl peptidase ( DPP )‐4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome ( CYP ) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic ( PK ) interaction of evogliptin with a CYP inhibitor, clarithromycin. Methods An open‐label, two‐phase, crossover study was conducted with 12 healthy subjects. On day 1, a single dose of evogliptin 5 mg was administered alone to assess the reference PK profile of evogliptin. On day 10, after a 2‐day pretreatment with clarithromycin, evogliptin 5 mg was administered again to evaluate the effect of CYP inhibition on the PK profile of evogliptin. Administration of clarithromycin continued until day 14. Blood sampling in the reference and test phases was performed until 96 and 168 hours after dosing, respectively for PK assays. Results Eleven of the 12 subjects completed the study, and their data were analysed. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the geometric mean peak plasma concentration (C max ) and area under the concentration‐time curve from time 0 extrapolated to infinity ( AUC 0‐∞ ) of evogliptin increased by 116.5% and 89.6%, respectively. What is new and conclusion Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.