Methods and Findings in Experimental and Clinical Pharmacology
Vol. 24, Suppl. A, 2002, pp. 33
ISSN 0379-0355
Copyright 2002 Prous Science, S.A.
CCC: 0379-0355/2002
http://www.prous.com

Almotriptan: From the Idea to International Recognition

J. Gras and P. Berga

Almirall Prodesfarma, Research Center, Barcelona, Spain

Triptans have been a breakthrough in the treatment of acute migraine, as they are more selective, efficacious and safer than their predecessors ergotamine and dihydroergotamine. However, some triptans have poor oral absorption, possess a high rate of headache recurrence or are contraindicated in patients with coronary artery disease. The objective of this paper is to summarize the main pharmacological features of almotriptan, a new triptan developed by Almirall Prodesfarma.

Almotriptan has nanomolar affinity for human
5-HT_1B, 5-HT_1D and 5-HT_1F receptors, weak affinity for 5-HT_1A and 5-HT₇ receptors and no significant affinity for over 20 other relevant pharmacological receptors. Almotriptan has shown efficacy and a good safety profile in animal models predictive of antimigraine activity in humans. In addition, almotriptan is devoid of any oncogenic, genotoxic and teratogenic effects in animal studies, at exposures far above its therapeutic levels in humans.

The pharmacokinetic studies performed in humans demonstrated that almotriptan is well absorbed after oral administration (absolute oral bioavailability of 70%) with peak plasma levels found at 1 to 3 h after administration and an elimination half-life of 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major routes, and 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 is no significant interaction when a single dose of almotriptan is administered with multiple doses of propranolol, fluoxetine and verapamil.

In clinical trials encompassing more than 4,800 migraine patients, almotriptan has demonstrated its efficacy in treating acute migraine. Indeed, at 2 h after oral administration of 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64% and 36%, respectively, differences from placebo being statistically significant. 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, when administered at 12.5 mg dose, almotriptan showed an incidence of adverse events that was not statistically different from placebo. The low incidence of central nervous system side effects and chest symptoms should be emphasized. Almotriptan is therefore the triptan of choice when good efficacy and high tolerability are required.

To summarize, almotriptan has a highly competitive pharmacological profile that warrants a significant place in the treatment of migraine.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 24, Suppl. A, 2002, pp. 33
ISSN 0379-0355 Copyright 2002 Prous Science, S.A. CCC: 0379-0355/2002 http://www.prous.com