In this randomized, double-blind, placebo-controlled, parallel-group study, patients received a single 50-mg oral dose of a 5-HT(1D) agonist, PNU-142633 (n = 34), or matching placebo (n = 35) during an acute migraine attack. No statistically significant treatment effects were observed at 1 and 2 h after dosing, even after stratifying by baseline headache intensity. At 1 and 2 h post-dose, 8.8% and 29.4% of the PNU-142633 group, respectively, and 8.6% and 40.0% of the placebo group, respectively, experienced headache relief; 2.9% and 8.8% of the PNU-142633 group and 0% and 5.7% of the placebo group were free of headache pain. Adverse events associated with PNU-142633 treatment included chest pain (two patients) and QTc prolongation (three patients). Results from this study suggest that anti-migraine efficacy is not mediated solely through the 5-HT(1D) receptor subtype, although this receptor may contribute, at least in part, to the adverse cardiovascular effects observed with 5-HT agonist medications.

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.

This study was designed to assess and compare the pharmacokinetics and tolerability of almotriptan, a 5-HT1B/1D agonist used to treat migraine attacks, in adolescents and adults. Healthy adolescents (n = 18) and adults (n = 18) received a single 12.5-mg dose of almotriptan after fasting overnight. Plasma and urinary almotriptan concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters of almotriptan were determined by non-compartment analysis. The 90% confidence interval (CI) approach was employed to assess age effects. Mean Cmax, tmax, area under the curve (AUC0- infinity ), half-life, and percentage excreted in urine were nearly identical for the two populations. Mean oral (CLPO) and renal (CLR) clearances were similar between the age groups; however, weight-corrected CLPO was approximately 32% higher (90% CI 16, 51) in adolescents compared with adults. The higher weight-corrected CLPO appeared to offset increases in exposure expected on the basis of lower body weight in adolescents. The findings were the same when a subgroup (n = 9) of 12-14-year-old children was compared with adults. The type, incidence and severity of adverse events were similar between the two age groups and were consistent with those reported previously during adult clinical trials. Based on these pharmacokinetic and tolerability findings, no dose adjustment for almotriptan would be required when treating patients as young as 12 years old.

Clinical Pharmacology & Therapeutics (2003) 73, P50–P50; doi: