Bentué-Ferrer Danièle, Tribut Olivier, Verdier Marie-Clémence
Laboratoire de Pharmacologie Biologique, CHU Pontchaillou, Rennes, France.
Therapie. 2010 May-Jun;65(3):233-40. doi: 10.2515/therapie/2010029. Epub 2010 Aug 11.
Valproic acid is an anticonvulsant drug available in France since 1967. It is a broad spectrum molecule indicated in various forms of epilepsy of the adult and the child, but it is also prescribed in the treatment of different other pathologies of nervous system. The divalproate sodium is indicated in the treatment of bipolar disorders. The valproic acid is marketed under various pharmaceutical forms, with different corresponding tmax values. But, whatever the administered preparation, the circulating active molecule is the ion valproate. Elimination half-life is from 11 to 20 h. Metabolization of valproate is important and represents its main route of elimination. Valpromide is comparable to a prodrug which metabolizes in valproate. The inter and intraindividual variability of the plasma concentrations are important. Several studies show a concentration-effect relationship, but two interventional trials ended in the lack of interest of the Therapeutic Drug Monitoring (TDM), although it is of current practice. However, numerous drug interactions may modify the plasma concentrations of valproate. The therapeutic range is from 50 to 100 mg/L (346-693 micromol/L). The level of proof of the interest of the TDM for this molecule was estimated in: recommended.
丙戊酸是一种自1967年起在法国上市的抗惊厥药物。它是一种广谱分子,可用于治疗成人和儿童的各种癫痫类型,同时也被用于治疗其他不同的神经系统疾病。双丙戊酸钠用于治疗双相情感障碍。丙戊酸有多种剂型上市,其相应的达峰时间(tmax)值各不相同。但是,无论使用何种制剂,循环中的活性分子都是丙戊酸离子。消除半衰期为11至20小时。丙戊酸的代谢作用很重要,是其主要的消除途径。丙戊酰胺类似于一种前体药物,可代谢为丙戊酸。血浆浓度的个体间和个体内变异性很大。多项研究显示了浓度-效应关系,但两项干预试验结果表明治疗药物监测(TDM)并无意义,尽管目前仍在使用TDM。然而,众多药物相互作用可能会改变丙戊酸的血浆浓度。治疗范围为50至100毫克/升(346 - 693微摩尔/升)。TDM对该分子有效性的证据水平评估为:推荐。