Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Department of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.
Drug Des Devel Ther. 2022 Dec 20;16:4301-4310. doi: 10.2147/DDDT.S383157. eCollection 2022.
Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics.
An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference.
Maximum concentration (C) and area under the plasma drug concentration-time curve (AUC) of evogliptin with and without co-administration of rifampicin were compared. Reference and test C and AUC values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration.
Rifampicin decreased the AUC of evogliptin by 61.8% without significantly affecting C. The mechanism underlying the decrease in AUC is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.
依格列净(DA-1229)是一种新型、强效、选择性二肽基肽酶 4(DPP-4)抑制剂,用于治疗 2 型糖尿病。本研究考察了利福平对依格列净药代动力学的影响。
12 名健康受试者参加了一项开放标签、交叉、单序列研究。受试者单剂量服用 5mg 依格列净后的第 1 天采集参比药代动力学样本。洗脱期后,从第 8 天到第 17 天,受试者每日给予利福平 600mg 一次,以充分诱导肝酶活性。第 17 天,受试者给予依格列净(5mg)单剂量,并合用利福平(600mg)。采用与参比相同的采样方案采集测试药代动力学样本。
比较了合用和不合用利福平时依格列净的最大浓度(C)和血浆药物浓度-时间曲线下面积(AUC)。依格列净参比和测试的 C 和 AUC 值分别为 4.70ng/mL 比 4.86ng/mL 和 153.97ng·h/mL 比 58.83ng·h/mL。所有不良事件均为轻度,认为与依格列净给药无关。
利福平使依格列净 AUC 降低 61.8%,但 C 无显著变化。AUC 降低的机制被认为是利福平诱导细胞色素 P450(CYP),特别是 CYP3A。合用依格列净和利福平并未显著改变不良事件,这些不良事件均不严重。然而,当与 CYP3A 诱导剂合用时,依格列净的剂量应谨慎考虑。