Lack of Pharmacokinetic Interaction Between the Antimigraine Compound, Almotriptan, and Propranolol in Healthy Volunteers

Abstract

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.

Cardiovascular effect of almotriptan in treated hypertensive patients

“…One subject received verapamil, which has been shown to increase almotriptan concentrations approximately 20%. 25 Propranolol has been shown not to affect almotriptan concentrations 26 ; atenolol (which 7 subjects received) would also be expected to have no effect. The most important consideration is that the higher plasma concentrations observed in this study may have an impact on the pharmacodynamic end points that were the primary focus of this trial.…”

Almotriptan in the treatment of migraine

“…Almotriptan has been tested for its potential pharmacokinetic interaction with several drugs, including MAO-A inhibitors (Fleishaker, Ryan, Jansat et al 2001), SSRIs (Fleishaker, Ryan, Carel et al 2001), β-adrenergic (Fleishaker, Sisson et al 2001) and calcium channel blocking agents (Fleishaker et al 2000), and ketokonazole (Fleishaker et al 2003), and even though some pharmacokinetic interaction was shown, including an increased plasma concentration of almotriptan, the authors did not find a clinically significant profile. Consequently, no dose adjustment is necessary when almotriptan is taken together with these drugs.…”

Focus on trial endpoints of clinical relevance and the use of almotriptan for the acute treatment of migraine

“…The almotriptan drug-drug interaction profile has been evaluated with regard to the calcium (Ca 2þ )-channel blocker verapamil (32), the b-blocker propranolol (33) and the selective serotonin reuptake inhibitor fluoxetine (34), all agents used for migraine prophylaxis, the antifungal agent ketoconazole (35) and the antidepressant moclobemide (36). Propranolol has been shown to inhibit the metabolic pathways of several drugs eliminated by the P450 pathway (37) and shares at least one elimination pathway with almotriptan, CYP2D6.…”