Gene polymorphisms involved in triptans pharmacokinetics and pharmacodynamics in migraine therapy

Abstract

Pharmacogenomic studies of triptans suggest that some genetic determinants influence drug response, but the complexity of the field calls for application of a systematic approach to genetic association studies, allowing identification of a therapy response prediction panel with adequate predictive power.

Textbook of Personalized Medicine

“…An observational study shows that serotonin transporter gene polymorphism STin2 VNTR confers an increased risk of inconsistent response to triptans in migraine patients (Terrazzino et al 2010 ). Although some genetic factors infl uence drug response, prediction of therapy response with adequate predictive power requires a systematic approach to genetic association studies due to complexity of the fi eld (Gentile et al 2011 ).…”

Clinical implications of neuropharmacogenetics

“…A few pharmacogenetics studies have investigated the response to triptans in migraine patients and have been reviewed elsewhere [141]. So far, most of these studies have failed to identify significant genetic association with drug response particularly with the serotonin receptor 5HT1B, one of the targets of these drugs.…”

Eletriptan in the management of acute migraine: an update on the evidence for efficacy, safety, and consistent response

“…Because of their longer half-lives, naratriptan and frovatriptan have a delayed onset of action with a more prolonged duration compared with the other fast-acting triptans, that display a rapid dosedependent efficacy with a higher risk of adverse effects and migraine recurrence [Markus and Mikko, 2007;Negro et al 2011] Triptan selection for each patient is a complex process that should take into account several variables: the characteristics of migraine attacks (speed of onset, intensity of pain, duration of the attack), the drug onset of action, the individual patient response and tolerance, the relief of associated symptoms, the headache recurrence, the consistency of the response, the different delivery systems and the patient characteristics (medical history, lifestyle and working habits) [Belvìs et al 2009]. Although the choice of a specific treatment is based mainly on the drug efficacy and safety profile, and therefore on its pharmacokinetic and pharmacodynamic properties [Géraud et al 2003], recently, the role of inherited and acquired genetic variations in drug response has also been highlighted [Gentile et al 2011;Negro et al 2011]. As shown in Table 1, eletriptan shows the most complex pharmacokinetic/ dynamic profiles among triptans and therefore a possible higher chance of bio and drug interactions (see http://www.drugbank.ca/).…”