Rapeport W G, Muirhead D C, Williams S A, Cross M, Wesnes K
Pfizer Central Research, Sandwich, Kent, United Kingdom.
J Clin Psychiatry. 1996;57 Suppl 1:24-8.
A double-blind, randomized, placebo-controlled study assessed the effects of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin in 30 healthy male volunteers.
All subjects received phenytoin throughout the study. The dose of phenytoin was 100 mg three times daily; steady-state trough plasma phenytoin concentrations were determined on Day 6. Concurrent treatment with sertraline (16 subjects) or placebo (13 subjects) was initiated on Day 8 and continued throughout the study in those subjects whose trough plasma phenytoin concentrations were between 5 and 20 micrograms/mL. The dose of sertraline was increased from 50 to 200 mg/day over 7 days; the 200-mg dose was then administered for 10 days. The plasma phenytoin concentration-time profile was determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24. Psychometric testing was done before and after dosing on Days 0, 7, and 24.
There were no significant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin. In addition, there was no indication that administration of phenytoin alone or concomitant administration of phenytoin and sertraline impaired cognitive function. Treatment-related side effects, primarily headache and nausea, were reported in 8 of 16 sertraline subjects and in 5 of 13 placebo subjects. Two subjects in the sertraline group withdrew because of side effects (rash), and 3 subjects in the placebo group withdrew because of side effects (rash and headache).
High dosages of setraline did not affect the pharmacokinetics or the pharmacodynamics of phenytoin in ths study performed in healthy volunteers.
一项双盲、随机、安慰剂对照研究评估了舍曲林对30名健康男性志愿者体内苯妥英钠药代动力学和药效学的影响。
在整个研究过程中，所有受试者均服用苯妥英钠。苯妥英钠剂量为每日3次，每次100毫克；在第6天测定稳态谷浓度下的血浆苯妥英钠水平。在第8天开始对苯妥英钠谷浓度在5至20微克/毫升之间的受试者同时给予舍曲林（16名受试者）或安慰剂（13名受试者），并在整个研究过程中持续给药。舍曲林剂量在7天内从50毫克/天增加至200毫克/天；然后给予200毫克剂量持续10天。在第7天舍曲林或安慰剂给药开始前以及第24天给药结束时测定血浆苯妥英钠浓度-时间曲线。在第0、7和24天给药前后进行心理测量测试。
舍曲林组和安慰剂组在苯妥英钠药代动力学参数方面无显著差异。此外，没有迹象表明单独服用苯妥英钠或同时服用苯妥英钠和舍曲林会损害认知功能。在16名服用舍曲林的受试者中有8名报告了与治疗相关的副作用，主要是头痛和恶心；在13名服用安慰剂的受试者中有5名报告了此类副作用。舍曲林组有2名受试者因副作用（皮疹）退出研究，安慰剂组有3名受试者因副作用（皮疹和头痛）退出研究。
在这项针对健康志愿者的研究中，高剂量舍曲林未影响苯妥英钠的药代动力学或药效学。
