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 con sequences of any interaction. Methods Twelve healthy volunteers received the following treatments in a ra ndomized, open-label, two-way crossover design (with a 1 week washout betwe en 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 m g 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 administra tion. Treatment effects on pharmacokinetics and vital signs were assessed b y 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 1 h(-1), P= 0.0001) when almotriptan was administered with moclobemid e. 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 wa s unaffected by moclobemide. No serious adverse events occurred and no clin ically significant vital sign changes were observed. Conclusions Moclobemide increased plasma concentrations of almotriptan on a verage by 37%, but the combined administration of these two compounds was w ell tolerated. The degree of interaction was much less than that seen previ ously for sumatriptan or zolmitriptan given with moclobemide.