Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults.
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.
Han
Tae H
TH
Merck Research Laboratories, North Wales, Pennsylvania, USA.
Blanchard
Rebecca L
RL
Palcza
John
J
McCrea
Jacqueline B
JB
Laethem
Tine
T
Willson
Kenneth
K
Xu
Yang
Y
Ermlich
Susan
S
Boyle
Janet
J
Lines
Christopher
C
Gutierrez
Maria
M
Van Bortel
Luc
L
Xiao
Alan J
AJ
Sinclair
Simon
S
Hickey
Lisa
L
Panebianco
Deborah
D
Murphy
M Gail
MG
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
D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; C525458:telcagepant