U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H21F7N4O3
Molecular Weight 534.4275
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APREPITANT

SMILES

C[C@]([H])(c1cc(cc(c1)C(F)(F)F)C(F)(F)F)O[C@]2([H])[C@]([H])(c3ccc(cc3)F)N(CCO2)Cc4nc(n[nH]4)O

InChI

InChIKey=ATALOFNDEOCMKK-OITMNORJSA-N
InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1

HIDE SMILES / InChI
Molecular Formula C23H21F7N4O3
Molecular Weight 534.4275
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Aprepitant (brand name: Emend (the brand name used in all English-speaking countries an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting. Aprepitant has been shown to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors.

CNS Activity

Originator

Merck
202
Curator's Comment:: # Merck & Ono Pharmaceutical

Approval Year

2003
63
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2577
Postoperative nausea and vomiting
Chemotherapy induced nausea and vomiting
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Neurokinin 1 receptor
Approved
7997
EMEND

Approved Use

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) EMEND, in combination with other antiemetic agents, is indicated for the: prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV): EMEND is indicated for the prevention of postoperative nausea and vomiting

Launch Date

1151539200000
Preventing
Neurokinin 1 receptor
Approved
7997
EMEND

Approved Use

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) EMEND, in combination with other antiemetic agents, is indicated for the: prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV): EMEND is indicated for the prevention of postoperative nausea and vomiting

Launch Date

1151625600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1354 ng/mL
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/21042544
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
4.3 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209296s000lbl.pdf
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
6.1 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209296s000lbl.pdf
130 mg single, intravenous
dose: 130 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
27759 ng × h/mL
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/21042544
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
27.8 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209296s000lbl.pdf
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
43.9 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209296s000lbl.pdf
130 mg single, intravenous
dose: 130 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14 h
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/21042544
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
125 mg single, oral
Dose: 125 mg
Route: oral
Route: single
Dose: 125 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31958446
unhealthy, 53 years (range: 23-73 years)
Health Status: unhealthy
Age Group: 53 years (range: 23-73 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/31958446
Sources:
https://pubmed.ncbi.nlm.nih.gov/31958446
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
Disc. AE: Dyspnea, Nerve injury, peripheral...
AEs leading to
discontinuation/dose reduction:
Dyspnea (2 patients)
Nerve injury, peripheral (1 patient)
Dyspnea (1 patient)
Hyperhidrosis (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Other AEs: Constipation, Diarrhea...
Other AEs:
Constipation (below serious, 14 patients)
Diarrhea (below serious, 7 patients)
Dry mouth (below serious, 7 patients)
Abdominal pain (below serious, 13 patients)
Weakness (below serious, 18 patients)
Nightmares (below serious, 2 patients)
Sleepiness (below serious, 2 patients)
Sweating (below serious, 8 patients)
Pain in extremity (below serious, 5 patients)
Dizziness (below serious, 7 patients)
Nervousness (below serious, 10 patients)
Nightmares (below serious, 2 patients)
Depression (below serious, 2 patients)
Sexual dysfunction (below serious, 3 patients)
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Other AEs: Hypoglycemia, Bruising...
Other AEs:
Hypoglycemia (serious, 1 patient)
Bruising (below serious, 1 patient)
Gastrointestinal pain (below serious, 3 patients)
Hypokalemia (below serious, 1 patient)
Diarrhea (below serious, 1 patient)
Musculoskeletal pain (below serious, 1 patient)
Fainting (below serious, 1 patient)
Renal bleeding (below serious, 1 patient)
Fibromyalgia (below serious, 1 patient)
Dizziness (below serious, 2 patients)
Constipation (below serious, 1 patient)
Rhinitis (below serious, 1 patient)
Headache (below serious, 2 patients)
Malaise (below serious, 1 patient)
Pain in limb (below serious, 1 patient)
Nosebleed (below serious, 1 patient)
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Other AEs: Anemia, Clot blood...
Other AEs:
Anemia (serious, 1 patient)
Clot blood (serious, 1 patient)
Hospital acquired pneumonia (serious, 1 patient)
Headache (below serious, 2 patients)
Hot flashes (below serious, 2 patients)
Nausea (below serious, 2 patients)
Paresthesia (below serious, 2 patients)
Wound dehiscence (below serious, 2 patients)
Wound infection (below serious, 6 patients)
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
AEs

AEs

AESignificanceDosePopulation
Dyspnea 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
Hyperhidrosis 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
Nerve injury, peripheral 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
Dyspnea 2 patients
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf
Nervousness below serious, 10 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Abdominal pain below serious, 13 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Constipation below serious, 14 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Weakness below serious, 18 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Depression below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Nightmares below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Nightmares below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Sleepiness below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Sexual dysfunction below serious, 3 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Pain in extremity below serious, 5 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Diarrhea below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Dizziness below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Dry mouth below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Sweating below serious, 8 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00896038
Bruising below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Constipation below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Diarrhea below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Fainting below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Fibromyalgia below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Hypokalemia below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Malaise below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Musculoskeletal pain below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Nosebleed below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Pain in limb below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Renal bleeding below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Rhinitis below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Dizziness below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Headache below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Gastrointestinal pain below serious, 3 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Hypoglycemia serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01149369
Headache below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Hot flashes below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Nausea below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Paresthesia below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Wound dehiscence below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Wound infection below serious, 6 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Anemia serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Clot blood serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Hospital acquired pneumonia serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT00888329
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1470

inhibitor
1172

inducer
657
substrate
865

inducer
343
substrate
1038

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1089
CYP1A2
892

CYP2C19
830

CYP2E1
567
P-gp
225
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1462
 moderate
yes (co-administration study)
Comment: 2.3 to 3.3 fold increase in mean AUC of orally coadministered midazolam;
Page: 7
P-gp
1255
 unlikely
P-gp
1255
 unlikely
CYP3A4
1462
 yes
CYP2C9
1362
 yes
weak (co-administration study)
Comment: no effect of drug on the plasma AUC of R(+) and S(-) warfarin; coadministration with tolbutamide (substrate) decreased AUC of tolbutamide by 23% (Day 4), 28% (Day 8), and 15% (Day 15);
Page: 7
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1470
 major
yes (co-administration study)
Comment: coadministration with ketoconazole (inhibitor) increased AUC of aprepitant by ~5-fold; coadministration with rifampin (inducer) decreased AUC of aprepitant by ~ 11-fold;
Page: 2
CYP1A2
892
 minor
CYP2C19
830
 minor
CYP2C9
865
 no
CYP2D6
1038
 no
CYP2E1
567
 no
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:499361
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:499361
MolPort
MolPort-006-392-367
https://www.molport.com/shop/molecule-link/MolPort-006-392-367
MolPort
MolPort-009-679-399
https://www.molport.com/shop/molecule-link/MolPort-009-679-399
ZINC
ZINC000027428713
http://zinc15.docking.org/substances/ZINC000027428713
PubMed

PubMed

TitleDatePubMed
Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.
1998 Nov 5
Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs.
2000 Mar 23
Central neurocircuitry associated with emesis.
2001 Dec 3
Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy.
2007 Apr
Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice.
2008 Jul
Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant.
2008 Sep
Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin.
2010 Nov
Case report: delirium due to a diltiazem-fentanyl CYP3A4 drug interaction.
2010 Nov-Dec
Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE.
2011 Apr 10
Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy.
2011 Aug
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clinical candidate.
2011 Feb 24
[Retrospective analysis of antiemetic effect in patients receiving cisplatin].
2011 Jul
Pemirolast reduces cisplatin-induced kaolin intake in rats.
2011 Jul 1
The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice.
2011 Jun 20
[The efficacy of aprepitant and palonosetron on cisplatin doublet in lung cancer].
2011 Oct
Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC).
2011 Sep
Use of high-dose cisplatin with aprepitant in an outpatient setting.
2012 Jul
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.
2015 Jun
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Patents

08133994
1

Sample Use Guides

In Vivo Use Guide
Prevention of Chemotherapy Induced Nausea and Vomiting:
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Aprepitant suppressed HIV Bal infection of macrophages. Treatment with aprepitant (10(-6) M) inhibited infection of macrophages with the AZT- resistant viruses (A018, A012) by 0.7 log(10). Aprepitant also suppressed infection of macrophages with RT inhibitor-resistant virus (TC 49 and TC 60) by 0.5 log(10). Furthermore, aprepitant significantly enhanced the anti-HIV activity of antiretrovirals (AZT, Efavirenz, and Indinavir) in HIV Bal-infected macrophages, and aprepitant inhibited CCR5 expression on macrophages, ranging from 50.5 to 29.6%. Donor heterogeneity was observed in antiviral activity and CCR5 receptor expression.
Monocytes isolated from healthy donors were cultured for 7 days and then treated with or without aprepitant (10(-6) M) for 2 h, followed by HIV infection with drug-resistant strains for 2 h.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:06:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:06:56 UTC 2021
Record UNII
1NF15YR6UY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APREPITANT
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
EMEND
Brand Name English
MK-0869
Code English
L-754,030
Code English
APREPITANT [EMA EPAR]
Common Name English
APREPITANT [USP-RS]
Common Name English
APREPITANT [VANDF]
Common Name English
APREPITANT [INN]
Common Name English
APREPITANT [ORANGE BOOK]
Common Name English
APREPITANT [EP MONOGRAPH]
Common Name English
APREPITANT [MART.]
Common Name English
3H-1,2,4-TRIAZOL-3-ONE, 5-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-1,2-DIHYDRO-
Systematic Name English
NSC-748825
Code English
CINVANTI
Brand Name English
3-(((2R,3S)-3-(P-FLUOROPHENYL)-2-(((.ALPHA.R)-.ALPHA.-METHYL-3,5-BIS(TRIFLUOROMETHYL)BENZYL)OXY)MORPHOLINO)METHYL)-.DELTA.(SUP 2)-1,2,4-TRIAZOLIN-5-ONE.
Common Name English
APREPITANT [WHO-DD]
Common Name English
APREPITANT [USP MONOGRAPH]
Common Name English
MK-869
Code English
APREPITANT [USAN]
Common Name English
APREPITANT [JAN]
Common Name English
APREPITANT [MI]
Common Name English
Classification Tree Code System Code
WHO-VATC QA04AD12
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
EMA ASSESSMENT REPORTS EMEND (AUTHORIZED: POSTOPERATIVE NAUSEA AND VOMITTING)
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
NDF-RT N0000175786
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
EMA ASSESSMENT REPORTS EMEND (AUTHORIZED: VOMITTING)
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
LIVERTOX 61
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
NDF-RT N0000010262
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
NCI_THESAURUS C267
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
WHO-ATC A04AD12
Created by admin on Fri Jun 25 21:06:56 UTC 2021 , Edited by admin on Fri Jun 25 21:06:56 UTC 2021
Code System Code Type Description
NDF-RT
N0000185506
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
PUBCHEM
135413536
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
IUPHAR
3490
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
NDF-RT
N0000182141
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
WIKIPEDIA
APREPITANT
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
NCI_THESAURUS
C49173
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
NDF-RT
N0000185507
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY Cytochrome P450 2C9 Inducers [MoA]
DRUG CENTRAL
230
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
MERCK INDEX
M2011
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY Merck Index
CAS
170729-80-3
Created by admin on Fri Jun 25 21:06:56 UTC 2021 , Edited by admin on Fri Jun 25 21:06:56 UTC 2021
PRIMARY
INN
8050
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
DRUG BANK
DB00673
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
ChEMBL
CHEMBL1471
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
EVMPD
SUB20017
Created by admin on Fri Jun 25 21:06:56 UTC 2021 , Edited by admin on Fri Jun 25 21:06:56 UTC 2021
PRIMARY
USP_CATALOG
1041904
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY USP-RS
MESH
C114556
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
RXCUI
358255
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY RxNorm
EPA CompTox
170729-80-3
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
FDA UNII
1NF15YR6UY
Created by admin on Fri Jun 25 21:06:57 UTC 2021 , Edited by admin on Fri Jun 25 21:06:57 UTC 2021
PRIMARY
Related Record Type Details
Structure of APREPITANT
EXCRETED UNCHANGED
Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted.
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
MINOR
SUBSTANCE-P RECEPTOR
TARGET -> INHIBITOR
ANTAGONIST
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
Structure of 2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL) MORPHOLINE, (2R,3S)-
METABOLITE -> PARENT
Structure of 6-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-5-(4-FLUOROPHENYL)3-MORPHOLINONE, (5S,6R)-
METABOLITE -> PARENT
Related Record Type Details
Structure of ENT-APREPITANT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
DESFLUORO APREPITANT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of APREPITANT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
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