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

This study was designed to assess the pharmacokinetics of almotriptan, a 5H T(1B/1D) agonist used to treat migraine attacks, when administered in the p resence 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 almo triptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-w ay crossover design. Plasma and urinary almotriptan concentrations were mea sured 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/m l vs. 44.3 +/- 10.9 ng/ml, p = 0.023). Mean AUG(0).(infinity) was not signi ficantly 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 inte rval for AUC(0).(infinity) was within the 80% to 125% limit for equivalence , but C-max was not (90% CI 106%-134% of the reference mean). Adverse event s were mild to moderate in intensity and no clinically significant treatmen t effects on vital signs or ECGs were observed. The results show that fluox etine has only a modest effect on almotriptan C-max. Concomitant administra tion of the two drugs is well tolerated and no adjustment of the almotripta n dose is warranted. (C) 2001 the American College of Clinical Pharmacology .