Gras Jordi, Llenas Jesús, Jansat Josep M, Jáuregui José, Cabarrocas Xavier, Palacios José M
Pharmacological Development Department, Almirall Prodesfarma, Research Center, Barcelona, Spain.
CNS Drug Rev. 2002 Fall;8(3):217-34. doi: 10.1111/j.1527-3458.2002.tb00226.x.
Almotriptan is a new anti-migraine agent with nanomolar affinity for human 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and 5-HT(7) receptors and no significant affinity for more than 20 other pharmacological receptors. Almotriptan was effective in animal models predictive of anti-migraine activity in humans and had a good safety profile in animal studies. From the toxicological point of view, almotriptan has a profile similar to that of other marketed triptans. In animal studies, at levels substantially higher than required for therapeutic activity in humans, almotriptan was devoid of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major metabolic route and by flavin monooxygenase as the minor route. No dose adjustment is required for gender or age, and only in the case of severe renal impairment the dose should not exceed 12.5 mg over a 24-h period. There was no significant interaction between a single dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. The efficacy of almotriptan in the treatment of acute migraine was demonstrated in clinical trials on more than 3000 patients with migraine. At two h after oral administration of almotriptan, 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64 and 36%, respectively. The effects of almotriptan were significantly better than those of placebo. When almotriptan was administered in the early phase of migraine, the percentage of pain-free patients at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study, the incidence of adverse events with almotriptan was not statistically different from that of placebo. Based on the available data, it appears that almotriptan is the triptan of choice when good efficacy and high tolerability are desired.
阿莫曲坦是一种新型抗偏头痛药物，对人5-HT(1B)、5-HT(1D)和5-HT(1F)受体具有纳摩尔亲和力，对5-HT(1A)和5-HT(7)受体亲和力较弱，对其他20多种药理受体无显著亲和力。阿莫曲坦在预测人类抗偏头痛活性的动物模型中有效，并且在动物研究中具有良好的安全性。从毒理学角度来看，阿莫曲坦的概况与其他已上市的曲坦类药物相似。在动物研究中，在远高于人类治疗活性所需的水平下，阿莫曲坦没有任何致癌、遗传毒性或致畸作用。阿莫曲坦口服吸收良好；其在人体内的绝对生物利用度为70%。给药后1至3小时达到血浆峰值水平；其消除半衰期为3至4小时。阿莫曲坦主要通过单胺氧化酶介导的氧化脱氨作用和细胞色素P450介导的氧化作用进行代谢，次要途径是通过黄素单加氧酶代谢。性别或年龄无需调整剂量，仅在严重肾功能损害的情况下，24小时内剂量不应超过12.5毫克。单剂量阿莫曲坦与多剂量的普萘洛尔、氟西汀或维拉帕米之间没有显著相互作用。超过3000例偏头痛患者的临床试验证明了阿莫曲坦治疗急性偏头痛的疗效。口服12.5毫克阿莫曲坦两小时后，疼痛缓解和无痛评分的患者百分比分别为64%和36%。阿莫曲坦的效果明显优于安慰剂。当在偏头痛早期给予阿莫曲坦时，两小时时无痛患者的百分比升至84%。在一项III期双盲安慰剂对照研究中，阿莫曲坦不良事件的发生率与安慰剂无统计学差异。根据现有数据，当需要良好疗效和高耐受性时，阿莫曲坦似乎是首选的曲坦类药物。
