Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract
Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract
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DOI：
10.1177/0091270006293767
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发表时间：
2007-01-01
影响因子：
2.9
通讯作者：
Lu, Ming
中科院分区：
文献类型：
--
作者：
Hinderling, Peter H.;Karara, Adel H.;Lu, Ming
本研究评估了法舒地尔（一种用于治疗稳定型心绞痛的新型Rho激酶抑制剂）在不同部位的胃肠道吸收，并评估了开发缓释制剂的可行性。10名健康男性志愿者入组，8名受试者完成了这项单剂量、开放标签、随机、5向交叉研究。40毫克盐酸法舒地尔作为溶液给药于回肠远端和升结肠，作为粉末给药于升结肠，作为速释片剂和溶液口服。所有治疗均耐受良好，未观察到严重不良事件。相对于口服溶液，M3的平均全身有效度分别为1.04（回肠远端，溶液）、1.14（升结肠，溶液）、1.27（升结肠，粉剂）和1.04（口服片剂），表明法舒地尔给药不同胃肠道部位后，M3的全身有效度相似。结果表明，一日一次的盐酸法舒地尔缓释制剂的研制应该是容易实现的。
This study evaluated the gastrointestinal absorption of fasudil, a novel Rho kinase inhibitor for the treatment of stable angina, at different sites using remote-controlled capsules and assessed the feasibility of developing an extended-release formulation. Ten healthy male volunteers were enrolled, and 8 subjects completed this single-dose, open-label, randomized, 5-way crossover study. Forty milligrams of fasudil HCl was administered as solution to the distal ileum and ascending colon, as powder to the ascending colon, and orally as an immediate-release tablet and solution. All treatments were well-tolerated and no serious adverse events were observed. The mean systemic availabilities of M3 relative to the oral solution were 1.04 (distal ileum, solution), 1.14 (ascending colon, solution), 1.27 (ascending colon, powder) and 1.04 (oral tablet), indicating similar systemic availability of M3 after administration of fasudil HCl to different gastrointestinal sites. The results suggest that development of a once-a-day extended-release formulation for fasudil HCl should be readily achievable.