Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers.
OBJECTIVE
To assess the interaction between almotriptan, a 5-HT1B/1D-receptor agonist used to treat migraine, and verapamil, an agent for migraine prophylaxis.


METHODS
Twelve healthy volunteers received the following treatments in a crossover 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 obtained on day 7. Almotriptan plasma concentrations were determined by liquid chromatography-tandem mass spectrometry; urine samples were analyzed by ultraviolet HPLC. Safety measures included blood pressure and pulse measurements, electrocardiography, and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters and vital sign data were made by ANOVA.


RESULTS
Mean almotriptan peak concentration and area under the plasma concentration-time curve were significantly higher and volume of distribution and oral clearance were significantly lower after coadministration of almotriptan 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 treatment on blood pressure or pulse were detected, with the exception of sitting systolic blood pressure at 2 hours after administration. However, the difference in mean change from baseline at this time point was only 8 mm Hg.


CONCLUSIONS
Verapamil modestly inhibited almotriptan clearance to a degree consistent with the modest contribution of CYP3A4 to almotriptan metabolism. 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.
Fleishaker
J C
JC
Clinical Pharmacology, Pharmacia & Upjohn, Inc., Kalamazoo, Mich 49007, USA. joseph.c.fleishaker@am.pnu.com
Sisson
T A
TA
Carel
B J
BJ
Azie
N E
NE
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy / Q000517:prevention & control; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D013607:Tablets; D014363:Tryptamines; D014700:Verapamil / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use / Q000652:urine
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D007211:Indoles; D017366:Serotonin Receptor Agonists; D013607:Tablets; D014363:Tryptamines; C409045:almotriptan; D014700:Verapamil