Pisani F, Haj-Yehia A, Fazio A, Artesi C, Oteri G, Perucca E, Kroetz D L, Levy R H, Bialer M
Department of Neurology, University of Messina, Italy.
Epilepsia. 1993 Sep-Oct;34(5):954-9. doi: 10.1111/j.1528-1157.1993.tb02117.x.
Six patients stabilized with carbamazepine (CBZ) therapy received an 8-day "add-on" supplement of valnoctamide (VCD), a tranquilizer available over the counter (OTC) in several European countries that exhibits promising anticonvulsant activity in animal models. During VCD intake, serum levels of the active CBZ metabolite, carbamazepine-10,11-epoxide (CBZ-E), increased fivefold from 1.5 +/- 0.7 micrograms/ml at baseline to 7.4 +/- 4.4 micrograms/ml after 4 days of VCD therapy and 7.7 +/- 3.1 micrograms/ml after 7 days of VCD therapy (means +/- SD, p < 0.01). In 4 patients, the increase in serum CBZ-E levels was associated with clinical signs of CBZ intoxication. CBZ-E levels returned to baseline after VCD therapy was discontinued. Serum CBZ levels remained stable throughout the study. The interaction observed in this study is similar to that described in patients treated with CBZ and valpromide (VPD, an isomer of VCD). In a mechanistic study, therapeutic concentrations of VCD inhibited hydrolysis of styrene oxide in human liver microsome preparations. Thus, VCD is a potent inhibitor of microsomal epoxide hydrolase (IC50 15 microM). There was a striking similarity between in vitro and in vivo inhibition potencies. In this study, VCD clearance was higher in epileptic patients (treated with CBZ) than in healthy subjects.
6例接受卡马西平（CBZ）治疗病情稳定的患者接受了为期8天的“附加”补充缬诺酰胺（VCD）治疗，VCD是一种在几个欧洲国家可在柜台购买的镇静剂，在动物模型中显示出有前景的抗惊厥活性。在服用VCD期间，活性CBZ代谢物卡马西平-10,11-环氧化物（CBZ-E）的血清水平从基线时的1.5±0.7微克/毫升增加了五倍，在VCD治疗4天后达到7.4±4.4微克/毫升，在VCD治疗7天后达到7.7±3.1微克/毫升（均值±标准差，p<0.01）。在4例患者中，血清CBZ-E水平的升高与CBZ中毒的临床体征相关。停用VCD治疗后，CBZ-E水平恢复到基线。在整个研究过程中，血清CBZ水平保持稳定。本研究中观察到的相互作用与接受CBZ和丙戊酰胺（VPD，VCD的异构体）治疗的患者中所描述的相似。在一项机制研究中，治疗浓度的VCD抑制了人肝微粒体制剂中环氧苯的水解。因此，VCD是微粒体环氧化物水解酶的强效抑制剂（IC50为15微摩尔）。体外和体内抑制效力之间存在显著相似性。在本研究中，癫痫患者（接受CBZ治疗）的VCD清除率高于健康受试者。
