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The Dose Proportionality of Telcagepant after Administration of Single Oral and Intravenous Doses in Healthy Adult Subjects
Version of Record online: 22 NOV 2010
© 2010, Archives of Drug Information
Archives of Drug Information
Volume 3, Issue 4, pages 55–62, December 2010
How to Cite
Han, T. H., Blanchard, R. L., Palcza, J., Martucci, A., Miller-Stein, C. M., Gutierrez, M., Panebianco, D., Rippley, R. K., Lines, C. and Murphy, M. G. (2010), The Dose Proportionality of Telcagepant after Administration of Single Oral and Intravenous Doses in Healthy Adult Subjects. Archives of Drug Information, 3: 55–62. doi: 10.1111/j.1753-5174.2010.00031.x
- Issue online: 7 DEC 2010
- Version of Record online: 22 NOV 2010
- Dose Proportionality
Introduction. Telcagepant (MK-0974) is a novel, orally active and selective CGRP receptor antagonist being investigated for acute treatment of migraine. Early clinical data suggested greater than dose proportional increases in exposure following oral administration. The aim of the present studies was to definitively characterize the oral and IV dose proportionality of telcagepant.
Methods. Healthy adult subjects were enrolled in two separate open-label randomized dose proportionality studies: 1) single oral dose crossover from 50 to 600 mg (N = 19); 2) single IV dose parallel group from 5 to 250 mg (N = 10 per dose). Blood samples were collected at time points from 0 to 48 hours postdose.
Results. Telcagepant was rapidly absorbed with a Tmax of approximately 1 to 2 hours after oral administration. The terminal half-life was approximately 8 to 9 hours after IV dosing and approximately 4 to 7 hours after oral dosing. Oral administration of telcagepant resulted in greater than dose proportional increases in exposure, while IV administration resulted in approximately dose proportional increases in exposure.
Conclusions. Telcagepant was generally well tolerated. Oral telcagepant exhibits non-linear pharmacokinetics.