Merck & Co., Inc., Kenilworth, New Jersey, USA.
Celerion Inc., Lincoln, Nebraska, USA.
Pharmacol Res Perspect. 2022 Feb;10(1):e00924. doi: 10.1002/prp2.924.
Gefapixant (MK-7264) is a first-in-class, selective antagonist of the P2X3 purinergic receptor currently being investigated as a therapeutic agent for the treatment of refractory or unexplained chronic cough. In non-clinical studies, gefapixant was eliminated primarily by renal excretion of the parent drug. The objective of this study was to assess the disposition of gefapixant in humans. The absorption, metabolism, and excretion profiles of gefapixant were assessed after oral administration of a single dose of [ C]gefapixant to six healthy adult males. Following a single-oral [ C]gefapixant dose to healthy adult males, the mass balance was achieved, with 98.9% of the administered radioactivity recovered in urine and feces. Elimination of gefapixant occurred primarily via renal excretion of the intact drug (64%); metabolism was a minor pathway of elimination of gefapixant (12% and 2% recovered in urine and feces, respectively). Single-dose administration of [ C]gefapixant 50 mg was generally well tolerated in healthy adult males. The fraction of the anticipated therapeutic oral dose of gefapixant absorbed is estimated to be at least 78%. Gefapixant is expected to be the major circulating drug-related material in plasma, and the majority of the dosed drug will be excreted unchanged in urine.
Gefapixant（MK-7264）是一种首创的、选择性的 P2X3 嘌呤能受体拮抗剂，目前正在研究用于治疗难治性或原因不明的慢性咳嗽。在非临床研究中，Gefapixant 主要通过肾脏排泄原型药物消除。本研究旨在评估 Gefapixant 在人体中的处置情况。在 6 名健康成年男性单次口服 [C]Gefapixant 后，评估了 Gefapixant 的吸收、代谢和排泄特征。在健康成年男性单次口服 [C]Gefapixant 后，达到了物质平衡，给予的放射性物质 98.9%在尿液和粪便中回收。Gefapixant 的消除主要通过肾脏排泄完整药物（64%）；代谢是 Gefapixant 消除的次要途径（分别在尿液和粪便中回收 12%和 2%）。在健康成年男性中，单次给予 [C]Gefapixant 50mg 通常具有良好的耐受性。预计 Gefapixant 的预期治疗口服剂量的吸收部分至少为 78%。Gefapixant 预计将是血浆中主要的循环药物相关物质，大部分给药药物将以原形从尿液中排泄。
