Pharmacokinetics and Pharmacodynamics of the Triptan Antimigraine Agents

Abstract

The current approach to antimigraine therapy comprises potent serotonin 5-HT1B/1D receptor agonists collectively termed triptans. Sumatriptan was the first of these compounds to be developed, and offered improved efficacy and tolerability over ergot-derived compounds. The development of sumatriptan was quickly followed by a number of 'second generation' triptan compounds, characterised by improved pharmacokinetic properties and/or tolerability profiles. Triptans are believed to effect migraine relief by binding to serotonin (5-hydroxy-tryptamine) receptors in the brain, where they act to induce vasoconstriction of extracerebral blood vessels and also reduce neurogenic inflammation. Although the pharmacological mechanism of the triptans is similar, their pharmacokinetic properties are distinct. For example, bioavailability of oral formulations ranges between 14% (sumatriptan) and 74% (naratriptan), and their elimination half-life ranges from 2 hours (sumatriptan and rizatriptan) to 25 hours (frovatriptan). Clearly, such diverse pharmacokinetic properties will influence the effectiveness of the compounds and favour the prescription of one over another in different patient populations. This article reviews the pharmacological properties of the triptans (time to peak plasma concentration, half-life, bioavailability and receptor binding) and relates these properties to efficacy and time of onset. It also considers the effects of concomitant medication, food, age and disease on the pharmacokinetics of the compounds. In addition, the relative merits, such as headache recurrence, tolerability and route of administration, are discussed. Finally, the performance of the triptans is considered in the context of direct head-to-head comparative trials that have assessed the efficacy profile of the compounds.

Preparation and Evaluation of Tubular Micelles of Pluronic Lecithin Organogel for Transdermal Delivery of Sumatriptan

“…Sumatriptan is a 5-hydroxy tryptamine 1D (5-HT1D)-receptor agonist, it was the first triptan available to use in the treatment of migraine. Sumatriptan is metabolized primarily by monoamine oxidase A and excreted in the urine and bile (18,19). Sumatriptan seems to act selectively on blood vessels located within the carotid circulation.…”

Cytochrome P450 and Non-Cytochrome P450 Oxidative Metabolism: Contributions to the Pharmacokinetics, Safety, and Efficacy of Xenobiotics

“…Given the predominance of the MAO-A-mediated pathway, the potential exists for MAO-A inhibitors such as moclobemide to inhibit sumatriptan metabolism and lead to clinically significant drug-drug interactions. Attempts have been made to mitigate the MAO-A metabolism by designing and developing the next-generation triptans that have very little contribution of MAO in their elimination (Jhee et al, 2001).…”

Parenteral vs. oral sumatriptan and naratriptan: plasma levels and efficacy in migraine. A comment

“…The oral bioavailability of sumatriptan is thus 20% lower during migraine attacks [8] and the Cmax C C for sumatriptan 300 mg is probably reduced to a similar extent during a migraine attack. For oral naratriptan the Tm T T ax increases from 2 h to 3.5 h during a migraine attack [21].…”