Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents -A comparative review

The current approach to antimigraine therapy comprises potent serotonin 5-H T1B/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 pr ofiles. Triptans are believed to effect migraine relief by binding to serot onin (5-hydroxy tryptamine) receptors in the brain, where they act to induc e vasoconstriction of extracerebral blood vessels and also reduce neurogeni c inflammation. Although the pharmacological mechanism of the triptans is similar, their ph armacokinetic properties are distinct. For example, bioavailability of oral formulations ranges between 14% (sumatriptan) and 74% (naratriptan), and t heir elimination half-life ranges from 2 hours (sumatriptan and rizatriptan ) to 25 hours (frovatriptan). Clearly, such diverse pharmacokinetic propert ies will influence the effectiveness of the compounds and favour the prescr iption of one over another in different patient populations. This article r eviews 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 effe cts of concomitant medication, food, age and disease on the pharmacokinetic s of the compounds. In addition, the relative merits, such as headache recu rrence, tolerability and route of administration, are discussed. Finally, t he performance of the triptans is considered in the context of direct head- to-head comparative trials that have assessed the efficacy profile of the c ompounds.