Why pharmacokinetic differences among oral triptans have little clinical importance: a comment

Abstract

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration–response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine.

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

“…Importantly, naratriptan, rizatriptan, and zolmitriptan also show similar, although less dramatic, sexrelated differences in peak and area under the curve plasma concentrations (Ferrari et al, 2011). It is not clear what, if any, relationship exists between the efficacy of these agents in migraine and the plasma concentration achieved (Ferrari et al, 2011;Vetvik and Macgregor, 2017). However, in comparison trials of frovatriptan versus rizatriptan, zolmitriptan, or almotriptan, all produced relatively similar efficacy to ameliorate or eliminate migraine headache, which was not different when men and women were compared (Franconi et al, 2014).…”

“…Frovatriptan, perhaps due to its long half-life, has a lower rate of headache recurrence than other triptans at 24 h post-administration, but also suffers from a lowered headache relief rating at 2 h (Jhee et al, 2001;Negro et al, 2011). Importantly, naratriptan, rizatriptan, and zolmitriptan also show similar, although less dramatic, sexrelated differences in peak and area under the curve plasma concentrations (Ferrari et al, 2011). It is not clear what, if any, relationship exists between the efficacy of these agents in migraine and the plasma concentration achieved (Ferrari et al, 2011;Vetvik and Macgregor, 2017).…”

Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology

“…Calcitonin gene-related peptide, a major player in migraine, causes dilation of the middle meningeal artery (MMA) in healthy volunteers, and sumatriptan reverses this dilation ( 22 ). Of note, pharmacokinetic parameters of triptans vary according to gender, with generally higher bioavailability in women and higher clearance rate in men ( 200 ). Gender-dependent dermal blood flow differences from capsaicin-induced release of CGRP ( 201 ) points to a specific mechanism underlying sexual dimorphism of migraine incidence.…”

Efficacy and tolerability of almotriptan in menstrual migraine: a comment

“…Differences between the various triptans, in particular almotriptan, have been rigorously evaluated and discussed through comparisons of several molecules of the triptan class and analyzing other parameters, including those from pharmacodynamics and pharmacokinetics [1,2]. In this issue, the question of the menstrual migraine therapy is addressed [3].…”