title: Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults.
abstract: Telcagepant is a novel, orally active, and selective calcitonin gene-related peptide receptor antagonist being developed for acute treatment of migraine with and without aura. Three separate clinical studies were conducted to evaluate the pharmacokinetics and tolerability of telcagepant following single oral doses in healthy young and elderly men and women and multiple oral doses in men. Telcagepant was rapidly absorbed with a time to maximum concentration of approximately 1.5 hours. The terminal half-life was approximately 6 hours. A greater than dose-proportional increase was observed in the area under the plasma concentration versus time curve from zero to infinity. Following twice-daily dosing, with each dose separated by 2 hours, steady state was achieved in approximately 3 to 4 days with an accumulation ratio of approximately 2. There were no clinically meaningful pharmacokinetic differences when compared across age and gender. Telcagepant was generally well tolerated up to single doses of 1200 mg and multiple doses of 400 mg twice daily.
authors.affiliation: Merck Research Laboratories, North Wales, Pennsylvania, USA.
authors.forename: Tae H
authors.initials: TH
authors.lastname: Han
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Blanchard
authors.forename: John
authors.initials: J
authors.lastname: Palcza
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: McCrea
authors.forename: Tine
authors.initials: T
authors.lastname: Laethem
authors.forename: Kenneth
authors.initials: K
authors.lastname: Willson
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Susan
authors.initials: S
authors.lastname: Ermlich
authors.forename: Janet
authors.initials: J
authors.lastname: Boyle
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.forename: Maria
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Luc
authors.initials: L
authors.lastname: Van Bortel
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Xiao
authors.forename: Simon
authors.initials: S
authors.lastname: Sinclair
authors.forename: Lisa
authors.initials: L
authors.lastname: Hickey
authors.forename: Deborah
authors.initials: D
authors.lastname: Panebianco
authors.forename: M Gail
authors.initials: MG
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D001381:Azepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; C525458:telcagepant