FOSAPREPITANT DIMEGLUMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H22F7N4O6P.2C7H17NO5
Molecular Weight	1004.8337
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.C[C@@H](O[C@H]1OCCN(CC2=NN(C(=O)N2)P(O)(O)=O)[C@H]1C3=CC=C(F)C=C3)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=VRQHBYGYXDWZDL-OOZCZQCLSA-N

InChI=1S/C23H22F7N4O6P.2C7H17NO5/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)40-20-19(13-2-4-17(24)5-3-13)33(6-7-39-20)11-18-31-21(35)34(32-18)41(36,37)38;2*1-8-2-4(10)6(12)7(13)5(11)3-9/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38);2*4-13H,2-3H2,1H3/t12-,19+,20-;2*4-,5+,6+,7+/m100/s1

HIDE SMILES / InChI

Molecular Formula	C7H17NO5
Molecular Weight	195.2136
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C23H22F7N4O6P
Molecular Weight	614.4066
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021549s024lbl.pdfhttp://www.drugbank.ca/drugs/DB06717
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021549s025lbl.pdf

Fosaprepitant (Emend for Injection (US), Ivemend (EU)) is a prodrug of Aprepitant. Once biologically activated, the drug acts as 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 is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. 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 (CI NV). Aprepitant has been shown in animal models 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. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing. Fosaprepitant is used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neurokinin 1 receptor 35 Target ID: CHEMBL249 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021549s025lbl.pdf	Antagonist 2778
Neurokinin 1 receptor 35 Target ID: CHEMBL249 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12590540	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Postoperative nausea and vomiting 29 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021549s024lbl.pdf	Preventing	Approved 8429	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 2006
Chemotherapy induced nausea and vomiting 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021549s024lbl.pdf	Preventing	Approved 8429	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 2006
Chemotherapy induced nausea and vomiting 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021549s025lbl.pdf	Secondary	Approved 8429	EMEND Approved Use EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist, indicated: • in combination with other antiemetic agents in patients 12 years of age and older and patients less than 12 years of age who weight at least 30 kg for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1) • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1) • for prevention of postoperative nausea and vomiting (PONV) in adults (1.2) Launch Date 2008
Postoperative nausea and vomiting 29 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021549s025lbl.pdf	Preventing	Approved 8429	EMEND Approved Use EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist, indicated: • in combination with other antiemetic agents in patients 12 years of age and older and patients less than 12 years of age who weight at least 30 kg for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1) • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1) • for prevention of postoperative nausea and vomiting (PONV) in adults (1.2) Launch Date 2008

C_max

Value	Dose	Analyte	Population
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

Value	Dose	Analyte	Population
44578 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17525168/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	FOSAPREPITANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.2 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17525168/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		FOSAPREPITANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17525168/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		FOSAPREPITANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse 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) n = 64 Health Status: unhealthy Condition: Cough Age Group: 53 years (range: 23-73 years) Sex: M+F Population Size: 64 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 Page: p. 27	unhealthy, adult n = 50 Health Status: unhealthy Age Group: adult Population Size: 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209296Orig1s000MedR.pdf Page: p. 27	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 Page: p. 27
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 n = 30 Health Status: unhealthy Condition: Post traumatic stress disorder Population Size: 30 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 n = 63 Health Status: unhealthy Condition: Chronic Nausea and Vomiting Population Size: 63 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 n = 34 Health Status: unhealthy Condition: Gynecologic Surgery Population Population Size: 34 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
150 mg single, intravenous Recommended Dose: 150 mg Route: intravenous Route: single Dose: 150 mg Sources: https://pubmed.ncbi.nlm.nih.gov/29873529	healthy, 33 n = 50 Health Status: healthy Age Group: 33 Sex: M+F Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/29873529	Disc. AE: Dyspnea... AEs leading to discontinuation/dose reduction: Dyspnea (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/29873529
150 mg single, intravenous Recommended Dose: 150 mg Route: intravenous Route: single Dose: 150 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: p.1	Disc. AE: Hypersensitivity reaction, Anaphylaxis... AEs leading to discontinuation/dose reduction: Hypersensitivity reaction Anaphylaxis Anaphylactic shock Infusion site reactions Thrombophlebitis Necrosis Vasculitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: p.1

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	substrate 1037 inducer 389 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP2C19 1478 CYP1A2 1524 CYP2E1 882 CYP2B6 810 CYP2C8 911 CYP 111	CYP1A2 1054 CYP2C19 991 CYP2E1 667 P-gp 1537	P-gp 257

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0	moderate		yes (co-administration study) Comment: 2.3 to 3.3 fold increase in mean AUC of orally coadministered midazolam; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 15.0	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_ClinPharmR.pdf Page: 29, 34	unlikely
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0	unlikely
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0	unlikely
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 9.0	weak [IC50 44.7 uM]	aprepitant 3
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	weak [IC50 >100 uM]	aprepitant 3
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 9.0	weak [IC50 >100 uM]	aprepitant 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	weak [IC50 >100 uM]	aprepitant 3
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	weak [IC50 >100 uM]	aprepitant 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	weak [Ki 108 uM]	aprepitant 3
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	weak [Ki 66 uM]	aprepitant 3
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 15, 16	weak		yes (co-administration study) Comment: fosaprepitant increased the AUC of midazolam by 1.8-fold; fosaprepitant increased diltiazem AUC by 1.4-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 15, 16
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 15.0	yes	aprepitant 3
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0	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); Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=7 Page: 7.0
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 9, 15	yes	aprepitant 3	yes (co-administration study) Comment: oral aprepitant decreased the AUC of tolbutamide by 23% on Day 4; fosaprepitant/aprepitant decreased warfarin exposure and prolongation of prothrombin time Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022023s017lbl.pdf Page: 9, 15
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	yes	aprepitant 3	yes (co-administration study) Comment: fosaprepitant/aprepitant increased pimozide exposure; fosaprepitant/aprepitant increased midazolam exposure; fosaprepitant/aprepitant increased dexamethazone exposure; ifosaprepitant/aprepitant increased methylprednisolone exposure Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	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; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8, 12	major	aprepitant 3	yes (co-administration study) Comment: ketoconazole completely inhibited metabolism of MK-0869 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8, 12
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	minor
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P1.pdf Page: 52.0	minor	aprepitant 3
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	minor
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	no	aprepitant 3
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	no	aprepitant 3
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21549_Emend_lbl.pdf#page=2 Page: 2.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P2.pdf Page: 8.0	no	aprepitant 3
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P1.pdf Page: 72.0	weak	aprepitant 3	no (co-administration study) Comment: lack of interaction between aprepitant with digoxin in clinical drug interaction study Sources: https://www.accessdata.fda.gov/drugsatfda_docs/NDA/2008/022023s000_PharmR_P1.pdf Page: 72.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:499361	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:499361
ChEBI	CHEBI:64321	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:64321
ChemicalBook	CB11515191	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB11515191
ChemicalBook	CB32557888	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32557888
ChemicalBook	CB7500857	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7500857
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
Selleck Chemicals	Aprepitant	http://www.selleckchem.com/products/Aprepitant.html
ZINC	ZINC000003939013	http://zinc15.docking.org/substances/ZINC000003939013
ZINC	ZINC000027428713	http://zinc15.docking.org/substances/ZINC000027428713
eMolecules	30153720	https://www.emolecules.com/cgi-bin/more?vid=30153720
eMolecules	36758241	https://www.emolecules.com/cgi-bin/more?vid=36758241
eMolecules	8763262	https://www.emolecules.com/cgi-bin/more?vid=8763262

PubMed

Title	Date	PubMed
		252160185
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	9804700
Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs.	2000 Mar 23	10737756
Central neurocircuitry associated with emesis.	2001 Dec 3	11749934
Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy.	2007 Apr	17389531
Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.	2007 Dec	18042005
Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects.	2007 Jul	17525168
Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant.	2008 Apr	18728837
Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting.	2008 Dec	19040346
Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice.	2008 Jul	18441096
Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.	2008 Nov	18983233
Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant.	2008 Sep	18719071
Lack of effect of aprepitant or its prodrug fosaprepitant on QTc intervals in healthy subjects.	2009 Aug	19608812
Recent trends in the impurity profile of pharmaceuticals.	2010 Jul	22247862
Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin.	2010 Nov	20718754
Case report: delirium due to a diltiazem-fentanyl CYP3A4 drug interaction.	2010 Nov-Dec	21112467
Pharmacokinetic evaluation of fosaprepitant dimeglumine.	2010 Oct	20795794
Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting.	2010 Oct 21	21042544
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	21383291
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	21229983
[Retrospective analysis of antiemetic effect in patients receiving cisplatin].	2011 Jul	21772101
Pemirolast reduces cisplatin-induced kaolin intake in rats.	2011 Jul 1	21539837
The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice.	2011 Jun 20	21466812
[The efficacy of aprepitant and palonosetron on cisplatin doublet in lung cancer].	2011 Oct	21996961
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	20623144
Use of high-dose cisplatin with aprepitant in an outpatient setting.	2012 Jul	21883567
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	25752796
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

Prevention of Chemotherapy Induced Nausea and Vomiting: 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg orally once daily in the morning on Days 2 and 3. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND (aprepitant capsules). Prevention of Postoperative Nausea and Vomiting: The recommended oral dosage of EMEND is 40 mg within 3 hours prior to induction of anesthesia EMEND may be taken with or without food.

Route of Administration: Oral

In Vitro Use Guide

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 Dec 15 16:18:29 GMT 2023` Edited by `admin` on `Fri Dec 15 16:18:29 GMT 2023`
Record UNII	D35FM8T64X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FOSAPREPITANT DIMEGLUMINE

Official Name

English

FOSAPREPITANT MEGLUMINE [MART.]

Common Name

English

MK-0517

Code

English

FOSAPREPITANT DIMEGLUMINE [ORANGE BOOK]

Common Name

English

FOSAPREPITANT DIMEGLUMINE [VANDF]

Common Name

English

D-GLUCITOL, 1-DEOXY-1-(METHYLAMINO)-, (3-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-2,5-DIHYDRO-5-OXO-1H-1,2,4-TRIAZOL-1-YL)PHOSPHONATE (2:1) (SALT)

Common Name

English

FOSAPREPITANT DIMEGLUMINE [MI]

Common Name

English

Fosaprepitant Meglumine [WHO-DD]

Common Name

English

FOCINVEZ

Brand Name

English

IVEMEND

Brand Name

English

BIS(1-DEOXY-1-(METHYLAMINO)-D-GLUCITOL) (3-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-2,5-DIHYDRO-5-OXO-1H-1,2,4-TRIAZOL-1-YL)PHOSPHONATE

Common Name

English

FOSAPREPITANT DIMEGLUMINE [USAN]

Common Name

English

FOSAPREPITANT MEGLUMINE [JAN]

Common Name

English

FOSAPREPITANT (AS DIMEGLUMINE)

Common Name

English

FOSAPREPITANT MEGLUMINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C267