| Indication |
For the acute treatment of migraine attacks with or without aura in adults. |
| Pharmacodynamics |
Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1D receptor agonists. Frovatriptan has no significant effects on GABAA
mediated channel activity and has no significant affinity for
benzodiazepine binding sites. Frovatriptan is believed to act on
extracerebral, intracranial arteries and to inhibit excessive dilation
of these vessels in migraine. Research has shown that migraine can be
caused by the swelling of blood vessels around the brain. Frovatriptan
eases the pain associated with migraine by narrowing these blood
vessels. Frovatriptan has one of the highest affinities for the 5-HT1B of the second-generation triptan agonists. |
| Mechanism of action |
Three distinct pharmacological actions have been implicated in the
antimigraine effect of the triptans: (1) stimulation of presynaptic
5-HT1D receptors, which serves to inhibit both dural
vasodilation and inflammation; (2) direct inhibition of trigeminal
nuclei cell excitability via 5-HT1B/1D receptor agonism in
the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or
pial vessels as a result of vascular 5-HT1B receptor agonism. |
| Absorption |
Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability. |
| Volume of distribution |
- 4.2 L/kg [males]
- 3 L/kg [females]
|
| Protein binding |
Binding to serum proteins is low (approximately 15%). Reversible binding to blood cells at equilibrium is approximately 60%. |
| Metabolism |
In vitro, cytochrome P450 1A2 appears to be the principal enzyme
involved in the metabolism of frovatriptan to several metabolites
including hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan,
hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan,
and several other minor metabolites. Desmethyl frovatriptan has lower
affinity for 5-HT1B/1D receptors compared to the parent
compound. The N-acetyl desmethyl metabolite has no significant affinity
for 5-HT receptors. The activity of the other metabolites is unknown. |
| Route of elimination |
Radiolabeled compounds excreted in urine were unchanged
frovatriptan, hydroxylated frovatriptan, N-acetyl desmethyl
frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl
frovatriptan, together with several other minor metabolites. Less than
10% of frovatriptan was excreted in urine after an oral dose. |
| Half life |
26 hours |
| Clearance |
- 220 mL/min [male receiving IV dose of 0.8 mg]
- 130 mL/min [Female receiving IV dose of 0.8 mg]
|
| Toxicity |
There is no direct experience of any patient taking an overdose of
Frovatriptan. The maximum single dose of frovatriptan given to male and
female patients with migraine was 40 mg (16 times the clinical dose)
and the maximum single dose given to healthy male subjects was 100 mg
(40 times the clinical dose) without significant adverse events. |
