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Evaluation of the Potential Pharmacokinetic Interaction between Almotriptan and Fluoxetine in Healthy Volunteers
Author(s) -
Fleishaker Joseph C.,
Ryan Kristi K.,
Carel Barbara J.,
Azie Nkechi E.
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122009917
Subject(s) - pharmacokinetics , cmax , fluoxetine , confidence interval , medicine , crossover study , pharmacology , anesthesia , serotonin , receptor , alternative medicine , pathology , placebo
This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/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 uri‐nary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan Cmax 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 AUC0 was not significantly affected by fluoxetine coadministration (353 ± 55.7ngh/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 AUC0 was within the 80% to 125% limit for equivalence, but Cmax 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 Cmax. Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted .