Lack of pharmacokinetic interaction between the antimigraine compound, almotriptan, and propranolol in healthy volunteers.
This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male (n = 10) and female (n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (ANOVA). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed (P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated.
Fleishaker
J C
JC
Clinical Pharmacology Unit, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49007, USA.
Sisson
T A
TA
Carel
B J
BJ
Azie
N E
NE
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D011433:Propranolol / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014363:Tryptamines; D014665:Vasodilator Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007211:Indoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014665:Vasodilator Agents; C409045:almotriptan; D011433:Propranolol