Effects of clarithromycin on the pharmacokinetics of evogliptin in healthy volunteers. (14th August 2017)

• Record Type: Journal Article
• Authors: Oh, E. S.; Choi, C.; Kim, C. O.; Kim, K. H.; Kim, Y. N.; Kim, S. J.; Park, M. S.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 42:Number 6(2017)
• Page Start: 689
• Page End: 694
• Publication Date: 2017-08-14
• Subjects: clarithromycin -- cytochrome P450 3A4 -- drug‐drug interaction -- evogliptin; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12604
• Languages: English
• ISSNs: 0269-4727

Abstract

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 (Cmax ) and area under the concentration‐time curve from time 0 extrapolated to infinity (AUC0‐∞ ) 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. Abstract : A clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. In 12 healthy subjects, a single dose of evogliptin 5 mg was administered alone or after a 2‐day pretreatment with clarithromycin to assess the PK profile of evogliptin. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the Cmax and AUC0‐∞ of evogliptin increased by 116.5% and 89.6% respectively.