Colucci R, Glue P, Holt B, Banfield C, Reidenberg P, Meehan J W, Pai S, Nomeir A, Lim J, Lin C C, Affrime M B
Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
J Clin Pharmacol. 1996 Jul;36(7):634-8. doi: 10.1002/j.1552-4604.1996.tb04228.x.
To assess the possible interaction between lamotrigine and felbamate, a double-blind, randomized, placebo-controlled, two-way crossover study was conducted in 21 healthy male volunteers. Volunteers were given lamotrigine (100 mg every 12 hours) and felbamate (1,200 mg every 12 hours) or matching placebo for 10 days during each period of the crossover. After morning administration on day 10, blood samples were obtained over 12 hours for measurement of lamotrigine. Felbamate increased the maximum concentration (Cmax) and and area under the concentration-time curve from time 0 to 12 hours (AUC0-12) of lamotrigine by 13% and 14%, respectively, compared with placebo. The 90% confidence intervals of the log-transformed pharmacokinetic parameters were within the 80-125% bioequivalance limits, however. Felbamate had no significant effect on the urinary excretion of lamotrigine (total), unconjugated lamotrigine, or the N-glucuronide. One volunteer discontinued the study after developing a rash while taking lamotrigine and placebo. All other adverse events were primarily related to the central nervous system and gastrointestinal tract, with a higher incidence reported during coadministration of lamotrigine and felbamate than with placebo. Overall, felbamate appears to have no clinically relevant effects on the pharmacokinetics of lamotrigine.
为评估拉莫三嗪与非氨酯之间可能的相互作用，对21名健康男性志愿者进行了一项双盲、随机、安慰剂对照的双向交叉研究。在交叉研究的每个阶段，志愿者接受拉莫三嗪（每12小时100毫克）和非氨酯（每12小时1200毫克）或匹配的安慰剂，持续10天。在第10天早晨给药后，在12小时内采集血样以测定拉莫三嗪。与安慰剂相比，非氨酯使拉莫三嗪的最大浓度（Cmax）以及0至12小时的浓度-时间曲线下面积（AUC0-12）分别增加了13%和14%。然而，对数转换后的药代动力学参数的90%置信区间在80%-125%的生物等效性限度内。非氨酯对拉莫三嗪的尿排泄（总量）、未结合的拉莫三嗪或N-葡萄糖醛酸苷没有显著影响。一名志愿者在服用拉莫三嗪和安慰剂时出现皮疹后退出了研究。所有其他不良事件主要与中枢神经系统和胃肠道有关，拉莫三嗪与非氨酯合用期间报告的发生率高于安慰剂。总体而言，非氨酯似乎对拉莫三嗪的药代动力学没有临床相关影响。
