Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers.
Aprepitant is the first NK1 receptor antagonist approved for use with corticosteroids and 5HT3 receptor antagonists to prevent chemotherapy-induced nausea and vomiting (CINV). The effective dose to prevent CINV is a 125-mg capsule on day 1 followed by an 80-mg capsule on days 2 and 3. Study 1 evaluated the bioavailability of the capsules and estimated the effect of food. The mean (95% confidence interval [CI]) bioavailabilities of 125-mg and 80-mg final market composition (FMC) capsules, as assessed by simultaneous administration of stable isotope-labeled intravenous (i.v.) aprepitant (2 mg) and FMC capsules, were 0.59 (0.53, 0.65) and 0.67 (0.62, 0.73), respectively. The geometric mean (90% CI) area under the plasma concentration time curve (AUC) ratios (fed/fasted) were 1.2 (1.10, 1.30) and 1.09 (1.00, 1.18) for the 125-mg and 80-mg capsule, respectively, demonstrating that aprepitant can be administered independently of food. Study 2 defined the pharmacokinetics of aprepitant administered following the 3-day regimen recommended to prevent CINV (125 mg/80 mg/80 mg). Consistent daily plasma exposures of aprepitant were obtained following this regimen, which was generally well tolerated.
Merck Research Laboratories, West Point, PA, USA.
Anup K
AK
Majumdar
Laura
L
Howard
Michael R
MR
Goldberg
Lisa
L
Hickey
Marvin
M
Constanzer
Paul L
PL
Rothenberg
Tami M
TM
Crumley
Deborah
D
Panebianco
Thomas E
TE
Bradstreet
Arthur J
AJ
Bergman
Scott A
SA
Waldman
Howard E
HE
Greenberg
Kathleen
K
Butler
A
A
Knops
Inge
I
De Lepeleire
Nicole
N
Michiels
Kevin J
KJ
Petty
D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077608:Aprepitant; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D064729:Neurokinin-1 Receptor Antagonists
D000932:Antiemetics; D002214:Capsules; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant