Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.
Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.
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DOI：
10.1002/cpdd.244
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发表时间：
2016-07
影响因子：
2
通讯作者：
Weiss M
中科院分区：
文献类型：
--
作者：
Erpenbeck VJ;Vets E;Gheyle L;Osuntokun W;Larbig M;Neelakantham S;Sandham D;Dubois G;Elbast W;Goldsmith P;Weiss M
我们评估了一种新型口服CRTH2拮抗剂苯丙哌胺(QAW039)在健康受试者中的药代动力学(PK)、安全性和耐受性。服药后1~3小时，血浆中苯丙哌胺浓度达高峰。浓度以多指数方式下降，随后出现明显的终末阶段(T1/2，∼20小时)。在4天内达到稳定状态，并有2倍的累积。部分消除是通过肾脏排泄(≤剂量的30%)和葡萄糖醛酸化作用。食物对扑热息痛的pk影响很小，单次和多次口服500 mg/d时耐受性良好。没有观察到剂量依赖性的不良事件，所有事件的严重程度都是轻微或中度的。考虑到体外药理学数据，系统浓度足够高，足以达到相关的目标占有率。总而言之，这些数据支持进一步发展为每日一次的过敏性疾病口服疗法。
We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1‒3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2, ∼20 hours). Steady state was achieved in 4 days with <2‐fold accumulation. Elimination was partly by renal excretion (≤30% of the dose) and glucuronidation. Food had minimal impact on the PK of fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose‐dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once‐daily oral therapy for allergic diseases.
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DOI：
10.1084/jem.193.2.255
发表时间：
2001-01-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirai H;Tanaka K;Yoshie O;Ogawa K;Kenmotsu K;Takamori Y;Ichimasa M;Sugamura K;Nakamura M;Takano S;Nagata K
通讯作者：
Nagata K
影响因子：
4.6
作者：
Tasaki, Mamoru;Kobayashi, Miki;Hirayama, Yoshitaka
通讯作者：
Hirayama, Yoshitaka
影响因子：
14.2
作者：
DOYLE, WJ;BOEHM, S;SKONER, DP
通讯作者：
SKONER, DP
DOI：
10.1073/pnas.0601574103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Cheng, K;Wu, TJ;Waters, MG
通讯作者：
Waters, MG
影响因子：
6.1
作者：
Barnes, N.;Pavord, I.;Perkins, C. M.
通讯作者：
Perkins, C. M.