Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers

Objective: To assess the interaction between almotriptan, a 5-HT1B/1D-recep tor agonist used to treat migraine, and verapamil, an agent for migraine pr ophylaxis. Methods: Twelve healthy volunteers received the following treatments in a c rossover design: (1) 120-mg sustained-release verapamil tablet twice daily for 7 days and one 12.5-mg almotriptan tablet on day 7 and (2) one 12.5-mg almotriptan tablet alone on day 7, Serial plasma and urine samples were obt ained on day 7, Almotriptan plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry; urine samples were analyzed by ul traviolet HPLC, Safety measures included blood pressure and pulse measureme nts, electrocardiography, and adverse event monitoring. Statistical compari sons of pharmacokinetic parameters and vital sign data were made by ANOVA. Results: Mean almotriptan peak concentration and area under the plasma conc entration-time curve were significantly higher and volume of distribution a nd oral clearance were significantly lower after coadministration of almotr iptan and verapamil compared with administration of almotriptan alone. The magnitudes of these differences were approximately 20%. Renal clearance was unaffected by verapamil coadministration, No significant effects of treatm ent on blood pressure or pulse were detected, with the exception of sitting systolic blood pressure at 2 hours after administration. However, the diff erence in mean change from baseline at this time point was only 8 mm Ng, Conclusions: Verapamil modestly inhibited almotriptan clearance to a degree consistent with the modest contribution of CYP3A4 to almotriptan metabolis m. This observation and the lack of effect of verapamil on the tolerability to almotriptan administration suggest that no reduction of the almotriptan dose is warranted.