Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females.
The pharmacokinetics and tolerability of intravenous (i.v.) 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 i.v. rizatriptan (0.5-5 mg) was well tolerated. The disposition kinetics of rizatriptan were linear for i.v. 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.
Lee
Y
Y
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486-0004, USA. yih_lee@merck.com
Ermlich
S J
SJ
Sterrett
A T
AT
Goldberg
M R
MR
Blum
R A
RA
Brucker
M J
MJ
McLoughlin
D A
DA
Olah
T V
TV
Zhao
J
J
Rogers
J D
JD
D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008881:Migraine Disorders / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013610:Tachycardia / Q000139:chemically induced; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014363:Tryptamines
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan