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Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females

The pharmacokinetics and tolerability of intravenous (IV) rizatriptan (MK‐0462), a novel 5‐HT1D/1B receptor agonist for the acute oral treatment of migraine, were examined in an open, single‐dose, four‐period, randomized crossover study in healthy females. Results of this study indicated that IV rizatriptan (0.5–5 mg) was well tolerated. The disposition kinetics of rizatriptan 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 (Cl) ranged between 859 and 941 mL min−1 from 0.5 to 2.5 mg, but dropped to slightly 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 (t1/2) was 1.5–2.2 h across all doses while mean residence time in the body (MRT) and steady state volume of distribution (Vss) of rizatriptan remained relatively invariant across doses. Urinary excretion of rizatriptan (Ue) ranged from 14.5 to 34.6% of dose. Copyright © 1998 John Wiley & Sons, Ltd.