Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females

The pharmacokinetics and tolerability of intravenous (IV) rizatriptan (MK-0 462), a novel 5-HT1D/1B receptor agonist for the acute oral treatment of mi graine, were examined in an open, single-dose, four-period, randomized cros sover study in healthy females. Results of this study indicated that IV riz atriptan (0.5-5 mg) was well tolerated. The disposition kinetics of rizatri ptan were linear for IV doses up to and including 2.5 mg. Relative to the 0 .5 mg dose, geometric mean dose-adjusted AUC ratios were 1.04, 1.09, and 1. 18 for 1, 2.5, and 5 mg doses, respectively. Apparent plasma clearance (CI) ranged between 859 and 941 mL min(-1) from 0.5 to 2.5 mg, but dropped to s lightly below 800 mL min(-1) for the 5 mg dose. Therefore, the elimination of rizatriptan appears somewhat dose dependent at the high end of this dose range. Mean plasma half-life (t(1/2)) was 1.5-2.2 h across all doses while mean residence time in the body (MRT) and steady state volume of distribut ion (V-ss) of rizatriptan remained relatively invariant across doses. Urina ry excretion of rizatriptan (U-e) ranged from 14.5 to 34.6% of dose. (C) 19 98 John Wiley & Sons, Ltd.