在许多国家,丙戊酸盐仅适用于癫痫,而其衍生物双丙戊酸钠(DVP)和丙戊酸钠(VPM)仅适用于双相情感障碍。DVP由丙戊酸钠和丙戊酸(VA)以1:1的摩尔比组成,并且VPM是在胃道中完全水解成VA的前药。不管是什么药,吸收的活性物质是丙戊酸离子。在这篇文章中,我们回顾了可能证明这些不同适应症合理的潜在原因.我们对疗效的比较研究进行了文献综述,药代动力学参数,VPA的副作用和成本,DVP,和VPM。我们发现只有比较VA和DVP的研究。八项功效研究均未发现癫痫或情绪障碍的差异。十项副作用研究报告了胃肠道反应方面的差异,但不一致。美国(US)产品特征和动力学比较研究总结报道了DVP和VA之间的生物等效性,但是DVP的Tmax更长,可能是由于其抗胃的盖伦形式。VPM产品特征和药代动力学研究总结显示生物利用度较低(80%vs.对于VA为100%)和延迟的Tmax。与VA相比,使用DVP或VPM需要额外费用(法国分别为177%和77%)。丙戊酸盐衍生物之间的适应症差异似乎没有道理。在双相情感障碍中VA和DVP之间的互换性似乎是可能的,在相同的剂量。当转换为丙戊酸盐时,VPM将需要更紧密的给药方案和剂量减少20%。
In many countries, valproate is indicated for epilepsy only, whereas its derivative divalproex (DVP) and
valpromide (VPM) are indicated for bipolar disorders only. DVP is composed of sodium valproate and valproic acid (VA) in a 1:1 molar ratio and VPM is a prodrug completely hydrolyzed in the gastric tract to VA. Whatever the drug, the absorbed and active substance is the valproate ion. In this article, we reviewed the potential reasons that might justify these different indications. We performed a literature review of comparative studies of efficacy, pharmacokinetic parameters, side effects and costs for VPA, DVP, and VPM. We found only studies comparing VA with DVP. None of the eight efficacy studies found differences in epilepsy or mood disorders. The ten studies of side effects reported a difference in terms of gastrointestinal effects, but inconsistently. The United States (US) summary of product characteristics and kinetic comparison studies reported bioequivalence between DVP and VA, but a longer Tmax for DVP, likely due to its gastro-resistant galenic form. VPM summary of product characteristics and pharmacokinetic studies revealed a lower bioavailability (80% vs. 100% for VA) and a delayed Tmax. There is an additional cost for using DVP or VPM as compared to VA (respectively +177% and +77% in France). The differences in indications between valproate derivatives do not seem justified. Interchangeability between VA and DVP in bipolar disorders seems possible, at identical dosage. VPM would require a closer dosing schedule and a 20% reduction in dosage when switching to valproate.