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Fleishaker, J.C. et al.

Fleishaker, Ryan, Jansat, Carel, Bell, Burke, Azie,

Effect of MAO-A inhibition on the pharmacokinetics of almotriptan, an antimigraine agent in humans.

AIMS: To assess the effect of a reversible MAO-A inhibitor, moclobemide, on the single-dose pharmacokinetics of almotriptan and assess the clinical consequences of any interaction. METHODS: Twelve healthy volunteers received the following treatments in a randomized, open-label, two-way crossover design (with a 1 week washout between treatments): (A) one 150 mg moclobemide tablet every 12 h for 8 days and one 12.5 mg almotriptan tablet on the morning of day 8; and (B) one 12.5 mg almotriptan tablet on day 8. Plasma almotriptan was quantified by h.p.l.c.-MS-MS, while urinary concentrations were measured by h.p.l.c.-u.v. Vital signs, ECGs, and adverse events were evaluated after almotriptan administration. Treatment effects on pharmacokinetics and vital signs were assessed by analysis of variance. RESULTS: Mean almotriptan AUC was higher (483 +/- 99.9 vs 352 +/- 75.4 ng ml-1 h, P = 0.0001) and oral clearance was lower (26.6 +/- 4.00 vs 36.6 +/- 5.89 l h-1, P = 0.0001) when almotriptan was administered with moclobemide. Mean half-life was longer (4.22 +/- 0.78 vs 3.41 +/- 0.45 h, P = 0.0002) after coadministration with moclobemide. Renal clearance of almotriptan was unaffected by moclobemide. No serious adverse events occurred and no clinically significant vital sign changes were observed. CONCLUSIONS: Moclobemide increased plasma concentrations of almotriptan on average by 37%, but the combined administration of these two compounds was well tolerated. The degree of interaction was much less than that seen previously for sumatriptan or zolmitriptan given with moclobemide.[1]

References

Effect of MAO-A inhibition on the pharmacokinetics of almotriptan, an antimigraine agent in humans. Fleishaker, J.C., Ryan, K.K., Jansat, J.M., Carel, B.J., Bell, D.J., Burke, M.T., Azie, N.E. British journal of clinical pharmacology. (2001) [Pubmed]

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