10.1177/0091270005284194 SWAN ET AL PHARMACOKINETIC PROFILE OF RIZATRIPTAN PHARMACOKINETICS Pharmacokinetic Profile of Rizatriptan 10-mg Tablet and 10-mg Orally Disintegrating Tablet Administered With or Without Water in Healthy Subjects: An Open-Label, Randomized, Single-Dose, 3-Period Crossover Study Suzanne K. Swan, MD, Harry Alcorn, Jr, PharmD, Anthony Rodgers, MS, Carolyn M. Hustad, PhD, Karen E. Ramsey, RPh, Susan Woll, MBA, and Franck Skobieranda, MD R izatriptan is a selective 5-HT 1B/1D agonist approved for the acute treatment of migraine headache. Rizatriptan orally disintegrating tablet (ODT) is a rap- idly disintegrating formulation of rizatriptan. Riza- triptan is completely absorbed after oral administra- tion. The mean oral absolute bioavailability of the rizatriptan tablet is approximately 45%, and mean peak plasma concentrations (C max ) are reached in ap- proximately 1 to 1.5 hours (time to maximum plasma concentration [t max ]). 1 The bioavailability and C max of rizatriptan were similar after administration of riza- triptan tablet and rizatriptan ODT, but the rate of ab- sorption is somewhat slower with rizatriptan ODT, with t max averaging 1.6 to 2.5 hours. 2 The area under the plasma concentration curve (AUC) of rizatriptan is ~30% higher in women than in men. 3 Food has no sig- nificant effect on the bioavailability of rizatriptan, but it delays the time to reach peak concentration by an hour. 4 The plasma half-life of rizatriptan in men and women averages 2 to 3 hours. 3 172 • J Clin Pharmacol 2006;46:172-178 This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally dis- integrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg riza- triptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geo- metric mean AUC 0-2h than ODTs and that ODTc has a greater geometric mean AUC 0-1h than tablet. A secondary end point was to compare the time of occurrence of the maximum riza- triptan plasma concentration (t max ) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC 0-2h compared with ODTs (33.84 h•ng/mL vs 18.83 h•ng/ mL; P < .001). ODTc had a slightly, but not statistically signifi- cantly, greater geometric mean AUC 0-1h compared with riza- triptan tablet (17.07 h•ng/mL vs 13.32 h•ng/mL). The median t max was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic differ- ence produces differential efficacy in a clinical setting. Keywords: Rizatriptan; pharmacokinetics; clinical trial; mi- graine medication Journal of Clinical Pharmacology, 2006;46:172-178 ©2006 the American College of Clinical Pharmacology From DaVita Clinical Research, Minneapolis, Minnesota (Dr Swan, Dr Alcorn); Hennepin County Medical Center, Minneapolis, Minnesota (Dr Swan); and Merck & Co, Inc, West Point, Pennsylvania (Mr Rodgers, Dr Hustad, Ms Ramsey, Ms Woll, and Dr Skobieranda). Submitted for publica- tion August 19, 2005; revised version accepted October 21, 2005. Ad- dress for reprints: Franck Skobieranda, MD, Merck & Co, Inc, PO Box 4, HM-323, West Point, PA 19486. DOI: 10.1177/0091270005284194