Ethanol does not significantly affect the bioavailability of almotriptan: an open, randomized, crossover, single-dose, phase I clinical trial in healthy volunteers

Objective: A number of clinical reports have revealed a link between the use of alcohol and the onset or exacerbation of migraine headaches. This open, randomized, crossover, single-dose, phase I clinical trial evaluated the possible pharmacokinetic interactions between a single oral dose of almotriptan 12.5 mg, a 5-HT 1B/1D receptor agonist for the acute treatment of migraine, and ethanol in 16 healthy male volunteers. Tolerability and safety of this combined treatment were also assessed. Methods: Subjects received a crossed oral dose of almotriptan (12.5 mg) with and without concomitant alcohol intake (target plasma concentration 0.8 g/kg) in two different treatment periods. Almotriptan was administered alone, while ethanol was diluted with orangejuice, which was also given to the control group. There was a washout period of 7 days between treatments. Plasma levels of almotriptan were analyzed using a sensitive and specific liquid chromatographic-tandem mass spectrometry method. Results: The 9 0 non-parametric confidence interval for the median t(max) of almotriptan plus ethanol compared to almotriptan alone (0.61/2.72) was outside the acceptable range (0.70-1.30), demonstrating that concomitant ethanol administration slightly increases the variability of absorption of almotriptan 12.5 mg. In contrast, the main bioavailability criteria parameters, C-max and AUC, which show the rate and extent of systemic absorption, were not affected by alcohol ingestion. Therefore, it is unlikely that concomitant ethanol intake would produce clinically relevant differences in the therapeutic effect of almotriptan at the dose studied here. Tolerability of treatments was good throughout the entire study period. Conclusions: Almotriptan 12.5 mg, with or without concomitant alcohol ingestion, showed similar plasma concentrations after a single dose in healthy volunteers with no clinically relevant drug-to-drug interactions.