Koivisto K, Sivenius J, Keränen T, Partanen J, Riekkinen P, Gothoni G, Tokola O, Neuvonen P J
Epilepsia. 1986 Jan-Feb;27(1):87-90. doi: 10.1111/j.1528-1157.1986.tb03506.x.
The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2-week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood-brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has proconvulsive properties in humans.
在这项开放性临床试验中，对27例对传统药物耐药的重度癫痫患者研究了一种新型牛磺酸衍生物——酞磺胺米隆的抗癫痫作用、对脑电图的影响及耐受性。在为期2周的对照期后，逐渐增加酞磺胺米隆的剂量，直至达到4.0g/天，并维持该剂量12天。酞磺胺米隆给药4周，然后在2周内逐渐撤药。在试验期间，随着酞磺胺米隆剂量增加，癫痫发作频率有统计学意义的显著增加，在试验的撤药阶段又再次下降。在6例退出试验的患者中，1例发生癫痫持续状态，2例患者癫痫发作次数增加或严重程度加重，因此必须停用酞磺胺米隆。脑电图记录及用于安全性评估的实验室数据均无变化。酞磺胺米隆能很好地透过血脑屏障，其主要代谢产物邻苯二甲酰亚胺基乙磺酰胺在脑脊液中的浓度约为血清浓度的一半。在酞磺胺米隆治疗期间，苯妥英浓度有统计学意义的显著升高，血清卡马西平浓度有显著下降。在本研究中未能证实动物实验中观察到的酞磺胺米隆的抗惊厥作用；相反，在酞磺胺米隆治疗期间癫痫发作有统计学意义的显著增加。其原因仍不清楚。所用剂量、显著的药物相互作用或患者情况似乎都不能完全解释所观察到的癫痫发作频率增加。一种解释可能是酞磺胺米隆在人体中具有促惊厥特性。
