Gijsman H, Kramer M S, Sargent J, Tuchman M, Matzura-Wolfe D, Polis A, Teall J, Block G, Ferrari M D
Leiden University Hospital, Netherlands.
Cephalalgia. 1997 Oct;17(6):647-51. doi: 10.1046/j.1468-2982.1997.1706647.x.
Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.
利扎曲普坦（MK - 462）是一种强效的5HT1D受体激动剂。这项多中心、双盲、安慰剂对照的门诊研究调查了利扎曲普坦（2.5毫克、5毫克和10毫克）不同剂量对急性偏头痛的临床疗效、安全性和耐受性。中度或重度偏头痛患者（n = 417）分别接受安慰剂治疗（n = 67）、利扎曲普坦2.5毫克治疗（n = 75）、5毫克治疗（n = 130）或利扎曲普坦10毫克治疗（n = 145）。在给药前（0小时）以及给药后0.5、1、1.5、2、3和4小时测量头痛严重程度、功能障碍和偏头痛症状。如果患者头痛疼痛为中度或重度，允许在2小时服用第二剂试验药物（即最初服用安慰剂→可选择服用利扎曲普坦10毫克作为第二剂；最初服用利扎曲普坦2.5毫克、5毫克或10毫克→可选择服用安慰剂作为第二剂）。在报告疼痛缓解的患者比例这一主要疗效指标上，观察到安慰剂、利扎曲普坦2.5毫克、5毫克和10毫克之间存在剂量反应关系，即给药后2小时头痛严重程度转变为“无疼痛或轻度疼痛”。这种关系在第一个记录时间点30分钟时就很明显，在1.5小时及之后具有统计学意义。在初始剂量后2小时这个主要时间点，报告疼痛缓解的患者比例，利扎曲普坦10毫克组为47.6%；利扎曲普坦5毫克组为45.4%；利扎曲普坦2.5毫克组为21.3%；安慰剂组为17.9%。服用利扎曲普坦10毫克的患者中有70%在4小时报告疼痛缓解。服用利扎曲普坦5毫克和10毫克的患者在给药后1.5小时和2小时的功能障碍明显低于服用安慰剂的患者。利扎曲普坦10毫克始终比5毫克更有效，尽管差异无统计学意义。最常见的临床不良事件是头晕、嗜睡和乏力/疲劳。没有患者因任何不良经历而停药，也没有严重不良事件。
