Wagner M L, Graves N M, Leppik I E, Remmel R P, Shumaker R C, Ward D L, Perhach J L
College of Pharmacy, University of Minnesota, Minneapolis.
Clin Pharmacol Ther. 1994 Nov;56(5):494-502. doi: 10.1038/clpt.1994.170.
Felbamate is a new antiepileptic drug approved for partial and secondarily generalized seizures.
Subjects with epilepsy (three men and seven women; age range, 20 to 39 years; weight range, 53 to 88 kg) who were previously stabilized with valproic acid, 9.5 to 31.7 mg/kg/day, received both 600 and 1200 mg felbamate twice a day in an open-label, randomized, crossover study.
Coadministration of 1200 or 2400 mg felbamate increased the mean valproic acid area under the curve (from 802.2 to 1025.4 and 1235.9 mg/hr/ml, respectively), peak concentrations (from 86.1 to 115.1 and 133.4 mg/ml, respectively), and average steady-state concentrations (from 66.9 to 85.5 and 103.0 mg/ml, respectively). No changes were observed in valproic acid time to peak concentration or protein binding. Average steady-state felbamate concentrations were 34.7 mg/ml for 600 mg administered twice daily and 61.2 mg/ml for 1200 mg administered twice daily.
When felbamate is added to a regimen of valproic acid, valproic acid doses may require reduction because coadministration of felbamate decreased steady-state valproic acid clearance (28% and 54%, respectively; p < 0.01).
非氨酯是一种新的抗癫痫药物，已被批准用于治疗部分性发作和继发性全身性发作。
在一项开放标签、随机、交叉研究中，之前使用丙戊酸（剂量为9.5至31.7毫克/千克/天）病情稳定的癫痫患者（3名男性和7名女性；年龄范围为20至39岁；体重范围为53至88千克），每天两次接受600毫克和1200毫克非氨酯治疗。
联合使用1200毫克或2400毫克非氨酯可增加丙戊酸的曲线下平均面积（分别从802.2增加至1025.4和1235.9毫克/小时/毫升）、峰值浓度（分别从86.1增加至115.1和133.4毫克/毫升）以及平均稳态浓度（分别从66.9增加至85.5和103.0毫克/毫升）。丙戊酸达到峰值浓度的时间或蛋白结合率未观察到变化。每天两次服用600毫克非氨酯时，平均稳态非氨酯浓度为34.7毫克/毫升；每天两次服用1200毫克非氨酯时，平均稳态非氨酯浓度为61.2毫克/毫升。
当将非氨酯添加到丙戊酸治疗方案中时，可能需要降低丙戊酸剂量，因为联合使用非氨酯会降低丙戊酸的稳态清除率（分别降低28%和54%；p < 0.01）。
