耐受性和药物动力学延迟推出富马酸二甲酯和不使用阿司匹林在健康的志愿者管理。

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谢赫SI, Nestorov我,罗素H, O 'Gorman J,黄R,米尔恩GL, Scannevin RH,洛瓦斯M,道森KT次方

耐受性和药物动力学延迟推出富马酸二甲酯和不使用阿司匹林在健康的志愿者管理。

其他。2013年10月,35 (10):1582 - 1594. e9。doi: 10.1016 / j.clinthera.2013.08.009。

PubMed ID

24139424 (在PubMed

]

文摘

背景:推迟发布富马酸二甲酯(DR-DMF) cytoprotective和抗炎特性,最近在美国被批准作为口服治疗复发的多发性硬化症。最常见的不良事件与DR-DMF冲洗和胃肠道(GI)事件的发生率随着时间推移而下降。摘要目的:本研究的目的是评估的耐受性和药代动力学(PK)概要DR-DMF有或没有伴随的乙酰水杨酸(阿司匹林)、环氧酶抑制剂。方法:健康志愿者(N = 56)被随机分配接受不同剂量方案DR-DMF或匹配的安慰剂有或没有与325毫克阿司匹林预处理4天。等离子体的活性代谢物水平天1和4一甲基延胡索酸酯进行了评估。冲洗和胃肠道事件评估使用patient-reported鳞片。潜在的冲洗介质进行了探讨。结果:DR-DMF显示安全性、耐受性和PK剖面与临床经验一致,没有积累的证据。与阿司匹林预处理对主PK参数没有影响,AUC0-10h或Cmax。冲洗严重性评估2 subject-reported等级量表,一般来说是比较温和,被评为最高的治疗。 Pretreatment with aspirin reduced flushing incidence and intensity without affecting GI events or the PK profile of DR-DMF. In some DR-DMF-treated individuals, plasma concentrations of a prostaglandin D2 (PGD2) metabolite were increased. CONCLUSIONS: In healthy volunteers, DR-DMF was well tolerated over 4 days of dosing, with a PK profile consistent with that previously reported and no evidence of accumulation. Aspirin pretreatment reduced the incidence and intensity of flushing without affecting GI events or the DR-DMF PK profile. Elevated levels of PGD2 in some DR-DMF-treated individuals suggest that flushing may be, at least in part, prostaglandin mediated. ClinicalTrials.gov identifier: ID: NCT01281111.

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药物

Diroximel延胡索酸酯