Oh E S, Choi C, Kim C O, Kim K H, Kim Y N, Kim S J, Park M S
Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Korea.
Department of Clinical Pharmacology and Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
J Clin Pharm Ther. 2017 Dec;42(6):689-694. doi: 10.1111/jcpt.12604. Epub 2017 Aug 14.
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.
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.
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 ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC ) of evogliptin increased by 116.5% and 89.6%, respectively.
Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.
依格列净（DA - 1229）是一种新型的具有高效力和选择性的二肽基肽酶（DPP）-4抑制剂，已在韩国获批用于治疗2型糖尿病。临床前研究表明，它由细胞色素（CYP）P450同工酶代谢。基于这些发现，设计了一项临床研究以调查依格列净与CYP抑制剂克拉霉素之间的药代动力学（PK）相互作用。
对12名健康受试者进行了一项开放标签、两阶段、交叉研究。在第1天，单独给予单剂量5毫克依格列净以评估依格列净的参考PK曲线。在第10天，在克拉霉素进行2天预处理后，再次给予5毫克依格列净以评估CYP抑制对依格列净PK曲线的影响。克拉霉素的给药持续至第14天。在参考期和试验期分别在给药后96小时和168小时进行血样采集以进行PK分析。
12名受试者中有11名完成了研究，并对他们的数据进行了分析。在存在克拉霉素的情况下，依格列净的暴露增加，且无任何严重不良事件，依格列净的几何平均血浆峰浓度（C）和从时间0外推至无穷大的浓度 - 时间曲线下面积（AUC）分别增加了116.5%和89.6%。
在健康受试者中，给予克拉霉素显著增加了依格列净的暴露量。
