Bioequivalence Study of Two Orodispersible Rizatriptan Formulations of 10 mg in Healthy Volunteers.

Mercè Cánovas,Francisco Polonio,Francesc Cabré

doi:10.3390/scipharm84030514

Abstract

The aim of the study was to assess the bioequivalence and tolerability of two different oral formulations of rizatriptan. A bioequivalence study was carried out in 40 healthy volunteers according to an open label, randomized, two-period, two-sequence, crossover, single dose, and fasting conditions design. The test and reference formulations were administered in two treatment days, separated by a washout period of seven days. Plasma concentrations of rizatriptan were obtained by the LC/MS/MS (Liquid chromatography tandem-mass spectrometry) method. Log-transformed AUC0-t (area under the plasma concentration-time curve from zero to the last measurable concentration) and Cmax (maximum plasma concentration) values were tested for bioequivalence based on the ratios of the geometric means (test/reference). The tmax (time to reach maximum plasma concentration) was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80%–125%. According to the European Guideline, it may therefore be concluded that the test formulation of rizatriptan 10 mg orodispersible tablet is bioequivalent to the reference formulation (Maxalt® Max 10 mg oral lyophilisate). The safety profile of both formulations was consistent with the summary of the product characteristics.

Highlights

A migraine is the most common headache disorder encountered in clinical practice
One subject dropped out of the study after the first period due to personal reasons; 39 completed the crossover design receiving a single dose of both formulations and were included in the pharmacokinetic analysis
Based upon a 90% confidence interval (CI) for the ratio of geometric LSmeans of logarithmically transformed AUC0-t and Cmax, the conclusion of bioequivalence can be made for the two orodispersible formulations of rizatriptan 10 mg

Summary

Introduction

A migraine is the most common headache disorder encountered in clinical practice. 25% of women and 9% of men are affected by this disorder. More than half of these patients complain of severe or very severe headache and of significant limitations of their social and work activities, with some confined to bed by the attacks [1]. Activation of the trigeminovascular system leads to release of vasoactive neuropeptides, resulting in vasodilation of the meningeal vessels and neurogenic inflammation. Both peripheral and central sensitizations have a role in migraine pain. The International Classification of Headache Disorders (ICHD-II) describes migraine as a recurrent headache disorder manifesting in attacks lasting 4–72 h. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia [2]

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