Bentué-Ferrer Danièle, Tribut Olivier, Verdier Marie-Clémence
CHU Pontchaillou, Laboratoire de Pharmacologie Biologique Rennes France.
Therapie. 2012 Mar-Apr;67(2):161-5. doi: 10.2515/therapie/2012013. Epub 2012 Aug 2.
Rufinamide is a third-generation antiepileptic drug, available since early 2010 in France. It is indicated in combination therapy in the Lennox-Gastaut syndrome from the age of 4. It has orphan drug status. The bioavailability of rufinamide is high, but decreases with the dose and increases with food intake. Rufinamide is not metabolized by cytochromes but hydrolyzed by a carboxylesterase in an inactive carboxylic derivative. Elimination is mainly renal. The half-life varies from 6 to 10h. Although established from relatively few studies, exposure efficacy and exposure toxicity relationships are argued. A plasma concentration of 15 mg/L, obtained with a standard regimen, reduces the number of seizures of 25%. Few factors of intrinsic variability are described. There are few clinically significant pharmacokinetic interactions and they concern combinations with other antiepileptic drugs, especially valproate. Although there is no validated therapeutic range, the level of evidence for this therapeutic drug monitoring has been estimated at "possibly useful".
卢非酰胺是一种第三代抗癫痫药物，自2010年初起在法国上市。它适用于4岁及以上Lennox-Gastaut综合征的联合治疗。它具有孤儿药地位。卢非酰胺的生物利用度较高，但会随剂量降低，随食物摄入增加。卢非酰胺不是由细胞色素代谢，而是由一种羧酸酯酶水解为无活性的羧酸衍生物。主要通过肾脏排泄。半衰期为6至10小时。尽管基于相对较少的研究确立，但暴露-疗效和暴露-毒性关系仍有争议。采用标准方案获得的血浆浓度为15 mg/L时，可使癫痫发作次数减少25%。描述的内在变异性因素较少。临床上显著的药代动力学相互作用较少，主要涉及与其他抗癫痫药物的联合使用，尤其是丙戊酸盐。虽然没有经过验证的治疗范围，但这种治疗药物监测的证据水平估计为“可能有用”。
