Effect of aprepitant on the pharmacokinetics of intravenous midazolam.
Oral aprepitant 125 mg, an antiemetic and a moderate inhibitor of the metabolism of oral midazolam, was assessed for interaction with intravenous midazolam in 12 subjects randomized to intravenous midazolam 2 mg +/- oral aprepitant 125 mg. The hypothesis was that midazolam AUC would not change by more than 2-fold (consistent with no more than weak inhibition) when midazolam + aprepitant was compared with midazolam alone. An AUC geometric mean ratio (midazolam + aprepitant/midazolam) with 90% confidence interval upper bound < or =2.0 (an increase in midazolam felt to be of modest clinical significance in the highly monitored perioperative period) was prespecified. Aprepitant increased intravenous midazolam AUC(0-infinity) 1.47-fold (90% confidence interval, 1.36-1.59), which fell within the prespecified criterion.
Majumdar
Anup K
AK
Merck Research Laboratories, West Point, Pennsylvania, USA.
Yan
Kerri X
KX
Selverian
Diana V
DV
Barlas
Suna
S
Constanzer
Marvin
M
Dru
James
J
McCrea
Jacqueline B
JB
Ahmed
Tuli
T
Frick
Glen S
GS
Kraft
Walter K
WK
Petty
Kevin J
KJ
Greenberg
Howard E
HE
D000328:Adult; D000932:Antiemetics / Q000009:adverse effects / Q000494:pharmacology*; D000077608:Aprepitant; D019540:Area Under Curve; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D009025:Morpholines / Q000009:adverse effects / Q000494:pharmacology*
D000932:Antiemetics; D009025:Morpholines; D000077608:Aprepitant; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam