首页> 外文OA文献 >Pharmacokinetics and Pharmacodynamics of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 (DPP-4) Inhibitor, after Single and Multiple Doses in Healthy Subjects
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Pharmacokinetics and Pharmacodynamics of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 (DPP-4) Inhibitor, after Single and Multiple Doses in Healthy Subjects

机译:在健康受试者进行单次和多次给药后,每周一次的双肽基肽酶-4(DPP-4)抑制剂奥格列汀的药代动力学和药效动力学。

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摘要

Abstract The pharmacokinetics (PK), and pharmacodynamics (PD) of omarigliptin, a novel once-weekly DPP-4 inhibitor, were assessed following single and multiple doses in healthy subjects. Absorption was rapid and food did not influence single dose PK. Accumulation was minimal and steady state was reached after 2-3 weeks. Weekly AUC and Cmax displayed dose proportionality within the dose range studied at steady state. The average renal clearance of omarigliptin was ~2 L/h. DPP-4 inhibition ranged from ~77-89% at 168 hours following the last of 3 once-weekly doses over the dose range studied. Omarigliptin resulted in ~2-fold increases in weighted average post-prandial active GLP-1. Omarigliptin acts by stabilizing active GLP-1, which is consistent with its mechanism of action as a DPP-4 inhibitor. Administration of omarigliptin was generally well tolerated in healthy subjects, and both the PK and PD profile support once-weekly dosing. A model-based assessment of QTc interval risk from the single ascending dose study indicated low risk of QTc prolongation within the likely clinical dose range
机译:摘要在健康受试者中,单次和多次服用奥格列汀,一种每周一次的新型DPP-4抑制剂,评估其药代动力学(PK)和药效学(PD)。吸收迅速并且食物不影响单剂量PK。 2-3周后,积累量很小,达到了稳态。每周AUC和Cmax显示在稳态下研究的剂量范围内的剂量比例。奥格列汀的平均肾脏清除率为〜2 L / h。在所研究的剂量范围内,每周3次给药的最后一次给药后168小时,DPP-4抑制作用范围为〜77-89%。奥格列汀导致餐后活性GLP-1的加权平均增加约2倍。奥格列汀通过稳定活性GLP-1发挥作用,这与其作为DPP-4抑制剂的作用机理相一致。在健康受试者中,奥格列汀的给药通常耐受良好,并且PK和PD曲线均支持每周一次的给药。来自单次剂量研究的基于模型的QTc间隔风险评估表明,在可能的临床剂量范围内,QTc延长的风险较低

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