| Indication |
For the acute treatment of migraine with or without aura in adults. |
| Pharmacodynamics |
Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor
agonist. In the anesthetized dog, eletriptan has been shown to reduce
carotid arterial blood flow, with only a small increase in arterial
blood pressure at high doses. While the effect on blood flow was
selective for the carotid arterial bed, decreases in coronary artery
diameter were observed. Eletriptan has also been shown to inhibit
trigeminal nerve activity in the rat. |
| Mechanism of action |
Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F
receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7
receptors, and little or no affinity for 5-HT2A, 5-HT2C, 5-HT3, 5-HT4,
5-HT5A and 5-HT6 receptors. Eletriptan has no significant affinity or
pharmacological activity at adrenergic alpha1, alpha2, or beta;
dopaminergic D1 or D2; muscarinic; or opioid receptors. Two theories
have been proposed to explain the efficacy of 5-HT receptor agonists in
migraine. One theory suggests that activation of 5-HT1 receptors located
on intracranial blood vessels, including those on the arteriovenous
anastomoses, leads to vasoconstriction, which is correlated with the
relief of migraine headache. The other hypothesis suggests that
activation of 5-HT1 receptors on sensory nerve endings in the trigeminal
system results in the inhibition of pro-inflammatory neuropeptide
release. |
| Absorption |
Well absorbed after oral administration with a mean absolute bioavailability of approximately 50%. |
| Volume of distribution |
|
| Protein binding |
Plasma protein binding is moderate and approximately 85%. |
| Metabolism |
In vitro studies indicate that eletriptan is primarily
metabolized by cytochrome P-450 enzyme CYP3A4. The N-demethylated
metabolite of eletriptan is the only known active metabolite. |
| Route of elimination |
Not Available |
| Half life |
The terminal elimination half-life of eletriptan is approximately 4 hours. |
| Clearance |
|
| Toxicity |
Based on the pharmacology of the 5-HT1B/1D agonists, hypertension
or other more serious cardiovascular symptoms could occur on overdose. |
