A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine

Abstract

Migraine is a common and often disabling neurovascular disorder. Changes in the metabolism and the central processing of serotonin, as well as abnormalities in the modulation of the central and peripheral trigeminal nociceptive pathways, have been shown to play signifi cant roles in migraine pathophysiology. Recent evidence suggests that a low serotonin state facilitates activation of the trigeminal nociceptive pathways. In addition, several pharmacological agents that modulate serotonin are used in the treatment of migraine. Specifi cally there are seven FDA approved, 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists, used for the acute abortive therapy of migraine. Zolmitriptan is one such triptan. Zolmitriptan is available as a tablet, orally disintegrating tablet and as a nasal spray. It is rapidly absorbed and detectable within the plasma, within 2 to 5 minutes for the nasal spray and within 15 minutes for the tablet. Zolmitriptan reaches peak plasma levels in 2-4 hours, with good levels maintained for up to 6 hours. Although the metabolism of zolmitriptan is predominantly hepatic, only 25% of zolmitriptan is bound to plasma proteins. Thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is very well tolerated with less than half of participants in clinical trials reporting adverse events, most of which were mild and transient. Although rare, serious cardiovascular events have been reported with all triptans. However, when patients are appropriately selected, zolmitriptan is both, a safe and effective acute migraine abortive agent. In this article, we will fi rst briefl y review the biological role of serotonin and the literature linking serotonin to migraine pathophysiology. This will be followed by a comprehensive review of the pharmacodynamics, pharmacokinetics and effi cacy of zolmitriptan. Finally, the clinical application of the use of zolmitriptan in migraine therapy will be discussed.

Applicability of RPMI 2650 and Calu-3 Cell Models for Evaluation of Nasal Formulations

“…The P app values for the two drugs reported with the Caco-2 cells are lower than those obtained with the RPMI 2650 cell line, but higher than those reported with the Calu-3 model [37,38]. Nevertheless, all the determined P app values indicate that these drugs are not highly permeable [29,30]. Most notably, the permeabilities of the investigated anti-migraine drugs do not differ in size order when compared to other drugs specifically intended for local therapy of the nasal mucosa instead of the systemic uptake.…”

Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans

“…In addition, we did not evaluate plasma levels of the different triptans, which act as substrates for different enzymes (see Table 3 ): some of these enzymes (e.g. CYP3A4 and CYP2D6) are differently expressed in men and women [ 22 ] suggesting that plasma levels of the various types of triptans may differ in the two sexes [ 23 – 30 ]. We think that all these limitations of our study are at least partially contrasted by the large number of subjects and migraine attacks included in the analysis.…”

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation

“…The absolute bioavailability of zolmitriptan is up to 40% for both oral and nasal dosage forms [6,7].…”