Armijo J A, Arteaga R, Valdizán E M, Herranz J L
Clinical Pharmacology Service, M. de Valdecilla University Hospital, University of Cantabria School of Medicine, Santander, Spain.
Clin Neuropharmacol. 1992 Dec;15(6):459-69. doi: 10.1097/00002826-199212000-00003.
The effects of adding vigabatrin (GVG) to the antiepileptic regimens of 16 children with refractory epilepsy have been studied. One-half of the regimens included sodium valproate (VPA). Parameters studied were seizure reduction, platelet GABA-T activity, and steady-state plasma concentrations (CSS) of GVG and VPA. Add-on GVG reduced the seizure frequency both in patients receiving VPA (from 42.9 to 4.5 seizures/month, p < 0.01) and in those without VPA (from 60.0 to 31.7 seizures/month, p < 0.05). GVG also reduced GABA-T activity in both groups (from 19.4 to 5.4, p < 0.001 and from 8.3 to 4.5 pmol/min/mg of protein, p < 0.05, respectively). Seizure reduction and GABA-T inhibition were greater in patients taking VPA than in those who were not. In patients receiving VPA, no significant changes were observed in VPA CSS values before and after the addition of GVG. On the other hand, no differences were found in GVG CSS values between patients with and without VPA. It is concluded that the coadministration of GVG to valproate reduces the frequency of seizures in refractory epileptic children and does not affect the steady-state plasma concentrations of either drug. Therefore, their association could be useful in clinical practice.
研究了在16例难治性癫痫患儿的抗癫痫治疗方案中添加氨己烯酸(GVG)的效果。一半的治疗方案包含丙戊酸钠(VPA)。研究的参数包括癫痫发作减少情况、血小板γ-氨基丁酸转氨酶(GABA-T)活性以及GVG和VPA的稳态血药浓度(CSS)。添加GVG后,接受VPA治疗的患者(癫痫发作频率从每月42.9次降至4.5次,p<0.01)以及未接受VPA治疗的患者(癫痫发作频率从每月60.0次降至31.7次,p<0.05)的癫痫发作频率均降低。GVG还降低了两组患者的GABA-T活性(分别从19.4降至5.4,p<0.001;从8.3降至4.5 pmol/min/mg蛋白,p<0.05)。服用VPA的患者癫痫发作减少和GABA-T抑制程度大于未服用者。在接受VPA治疗的患者中,添加GVG前后VPA的CSS值未观察到显著变化。另一方面,接受和未接受VPA治疗的患者之间GVG的CSS值没有差异。结论是,GVG与丙戊酸盐联合使用可降低难治性癫痫患儿的癫痫发作频率,且不影响两种药物的稳态血药浓度。因此,它们的联合应用在临床实践中可能有用。