Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females

✍ Scribed by Yih Lee; Susan J. Ermlich; Andrew T. Sterrett; Michael R. Goldberg; Robert A. Blum; Mary J. Brucker; Debra A. McLoughlin; Timothy V. Olah; Jamie Zhao; J. Douglas Rogers

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 120 KB
• Volume: 19
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199812)19:9<577::aid-bdd136>3.0.co;2-w

✦ Synopsis

The pharmacokinetics and tolerability of intravenous (IV) rizatriptan (MK-0462), a novel 5-HT 1D/1B receptor agonist for the acute oral treatment of migraine, were examined in an open, singledose, 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 (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 distribution (V ss ) of rizatriptan remained relatively invariant across doses. Urinary excretion of rizatriptan (U e ) ranged from 14.5 to 34.6% of dose.