Wagner M L, Remmel R P, Graves N M, Leppik I E
College of Pharmacy, University of Minnesota, Minneapolis 55455.
Clin Pharmacol Ther. 1993 May;53(5):536-43. doi: 10.1038/clpt.1993.67.
Felbamate is a novel antiepileptic drug that is now available in the United States. During a previous double-blind, crossover, placebo-controlled safety and efficacy study, concomitant phenytoin concentrations increased, whereas carbamazepine concentrations decreased. We evaluated the effect of felbamate on the concentrations of carbamazepine and of its major metabolites, carbamazepine-10,11-epoxide (epoxide) and carbamazepine-trans-10,11-diol (diol) in 26 patients. After the addition of felbamate, mean epoxide concentrations increased from 1.8 micrograms/ml during placebo or baseline periods to 2.4 micrograms/ml during felbamate treatment (p < 0.05); there was no significant change in diol concentrations. Mean carbamazepine concentrations decreased from 7.5 micrograms/ml during placebo treatment to 6.1 micrograms/ml during felbamate treatment (p < 0.05). Mechanisms that could account for the increase in steady-state epoxide concentrations are induction of carbamazepine metabolism to epoxide, inhibition of the conversion of epoxide to diol, or both.
非氨酯是一种新型抗癫痫药物，目前已在美国上市。在之前一项双盲、交叉、安慰剂对照的安全性和有效性研究中，苯妥英的伴随浓度升高，而卡马西平的浓度降低。我们评估了非氨酯对26例患者卡马西平及其主要代谢产物卡马西平-10,11-环氧化物（环氧化物）和卡马西平反式-10,11-二醇（二醇）浓度的影响。添加非氨酯后，环氧化物平均浓度从安慰剂或基线期的1.8微克/毫升增加到非氨酯治疗期的2.4微克/毫升（p<0.05）；二醇浓度无显著变化。卡马西平平均浓度从安慰剂治疗期的7.5微克/毫升降至非氨酯治疗期的6.1微克/毫升（p<0.05）。可能导致稳态环氧化物浓度升高的机制包括卡马西平代谢为环氧化物的诱导、环氧化物向二醇转化的抑制或两者兼有。
