Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers.

This study was designed to assess the pharmacokinetics of almotriptan, a 5HT 1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine. Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan C max was significantly higher following combination treatment with fluoxetine (52.5 ± 11.9 ng/ml vs. 44.3 ± 10.9 ng/ml, p = 0.023). Mean AUC 0- ∞ was not significantly affected by fluoxetine coadministration (353 ± 55.7 ng.h/ml vs. 333 ± 33.6 ng.h/ml, p = 0.059), Confidence interval analysis (90%) of log-transformed pharmacokinetic parameters showed that the confidence interval for AUC 0- ∞ was within the 80% to 125% limit for equivalence, but C max was not (90% CI 106%-134% of the reference mean). Adverse events were mild to moderate in intensity, and no clinically significant treatment effects on vital signs or ECGs were observed. The results show that fluoxetine has only a modest effect on almotriptan C max . Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted.