Rufinamide:癫痫患者临床药物动力学和量效关系。

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Perucca E, Cloyd而言J,奎奇立D, Fuseau E

Rufinamide:癫痫患者临床药物动力学和量效关系。

Epilepsia。2008年7月,49 (7):1123 - 41。doi: 10.1111 / j.1528-1167.2008.01665.x。

PubMed ID

18503564 (在PubMed

]

文摘

Rufinamide是一个新的,口服抗癫痫药物(AED),已被发现是有效的治疗局部癫痫放攻击与Lennox-Gastaut综合症有关。当用食物,rufinamide相对较好吸收在低剂量范围内,与大约dose-proportional等离子体浓度高达1600毫克/天,但低于dose-proportional等离子体浓度更高剂量由于减少口服生物利用度。Rufinamide不是广泛与血浆蛋白。在重复给药,在2天内达到稳定状态,符合其消除半衰期为6 - 10 h。表观分布容积(V (d) / F)和明显的口腔间隙(CL / F)与体型有关,最好的预测被身体表面积。Rufinamide不是基质细胞色素P450 (CYP450)通过由羧酸酯酶水解酶和广泛代谢药物活性的羧酸衍生物,在尿液中排出。Rufinamide药物动力学不影响肾功能受损。潜在的差异rufinamide药物动力学系统考察了儿童和成人之间没有正式的研究。尽管人口药代动力学建模表明,在缺乏互动comedication rufinamide CL / F可能在儿童比成人高,比较有意义的跨年龄组的数据是复杂的,与年龄相关的剂量差异和接受药物的患者比例增加或减少rufinamide CL / F。一项研究调查的影响rufinamide CYP3A4衬底三唑仑的药物代谢动力学和相互作用研究表明,口服避孕药rufinamide有enzyme-inducing潜力的人。发现从群体药代动力学建模表明,rufinamide不修改CL / F(托吡酯或丙戊酸,但可能略有增加卡马西平和拉莫三嗪的CL / F稍微降低CL / F(苯巴比妥和苯妥英(所有预测变化< 20%)。 These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but valproic acid may increase plasma rufinamide concentrations, especially in children in whom plasma rufinamide concentrations could be increased substantially. Conversely, comedication with carbamazepine, vigabatrin, phenytoin, phenobarbital, and primidone was associated with a slight-to-moderate decrease in plasma rufinamide concentrations, ranging from a minimum of -13.7% in female children comedicated with vigabatrin to a maximum of -46.3% in female adults comedicated with phenytoin, phenobarbital, or primidone. In population modeling using data from placebo-controlled trials, a positive correlation has been identified between reduction in seizure frequency and steady-state plasma rufinamide concentrations. The probability of adverse effects also appears to be concentration-related.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Rufinamide	细胞色素P450 3 a4	蛋白质	人类	未知的	诱导物	细节