Netupitant

Netupitant

Clinical data
Trade names	Akynzeo
Routes of administration	Oral
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	>60% (estimated)
Protein binding	>99%
Metabolism	mainly CYP3A4; also CYP2D6 and CYP2C9
Biological half-life	88 hours
Excretion	71% (faeces)
Identifiers
IUPAC name 2-[3,5-Bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinyl]propanamide
CAS Number	290297-26-6
PubChem CID	6451149
DrugBank	DB09048
ChemSpider	4953629
UNII	7732P08TIR
KEGG	D05152
ChEBI	CHEBI:85155
ChEMBL	CHEMBL206253
Chemical and physical data
Formula	C30H32F6N4O
Molar mass	578.59 g/mol
3D model (JSmol)	Interactive image
SMILES Cc1ccccc1c2cc(ncc2N(C)C(=O)C(C)(C)c3cc(cc(c3)C(F)(F)F)C(F)(F)F)N4CCN(CC4)C
InChI InChI=1S/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3 Key:WAXQNWCZJDTGBU-UHFFFAOYSA-N

Netupitant is an antiemitic drug. In the United States, the combination drug netupitant/palonosetron (trade name Akynzeo) is approved by the Food and Drug Administration for prevention of acute and delayed chemotherapy-induced nausea and vomiting, including highly emetogenic chemotherapy such as with cisplatin. In Europe, it is approved by the European Medicines Agency for the same indication.

Side effects of the combination netupitant/palonosetron are similar to palonosetron alone, so that no common side effects can be attributed to netupitant.

Netupitant blood plasma levels are expected to increase when combined with inhibitors of the liver enzyme CYP3A4 and lowered when combined with inductors of this enzyme.

Being a CYP3A4 inhibitor itself, netupitant could also increase plasma levels of pharmaceuticals that are metabolized by CYP3A4. This effect has been observed with dexamethasone, the anti-cancer drugs docetaxel and etoposide, and to a minor (not clinically significant) extent with levonorgestrel, erythromycin and midazolam.

Netupitant is a selective NK₁ receptor antagonist.

Bioavailability is estimated to be over 60% for orally taken netupitant. Highest blood plasma concentrations are reached five hours after application. Availability is moderately (10–20%) increased when taken after a fatty meal. Netupitant and its main metabolites (called M1 and M3) are bound to plasma proteins to more than 99%, and M2 protein binding is 97%.