Details of the Drug Combination

General Information of Drug Combination (ID: DCSPE9V)

Drug Combination Name
Palonosetron Netupitant
Indication
Disease Entry Status REF
Chemotherapy-induced Nausea and Vomiting (CINV) Phase 2 [1]
Component Drugs Palonosetron   DMBHMOX Netupitant   DMEKAYI
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Palonosetron
Disease Entry ICD 11 Status REF
Nausea MD90 Approved [2]
Vomiting MD90 Approved [3]
Palonosetron Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 3A receptor (HTR3A) TTPC4TU 5HT3A_HUMAN Antagonist [5]
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Palonosetron Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
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Palonosetron Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [8]
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Indication(s) of Netupitant
Disease Entry ICD 11 Status REF
Chemotherapy-induced nausea MD90 Phase 3 [4]
Netupitant Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Substance-P receptor (TACR1) TTZPO1L NK1R_HUMAN Antagonist [9]
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Netupitant Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [11]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Nausea Post Chemotherapy DCUR6PZ N. A. Phase 2 [12]
Chemotherapy-induced nausea DCN6O9G N. A. Phase 1 [13]
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References

1 ClinicalTrials.gov (NCT03204279) PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7486).
3 Palonosetron FDA Label
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5742).
5 Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
6 Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37.
7 Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.
8 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
9 Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
10 Complementary pharmacokinetic profiles of netupitant and palonosetron support the rationale for their oral fixed combination for the prevention of chemotherapy-induced nausea and vomiting. J Clin Pharmacol. 2019 Apr;59(4):472-487.
11 Effect of netupitant, a highly selective NK?receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives. Support Care Cancer. 2013 Oct;21(10):2879-87.
12 ClinicalTrials.gov (NCT04669132) Efficacy of Olanzapine, Netupitant and Palonosetron in Controlling Nausea and Vomiting Associated With Highly Emetogenic Chemotherapy in Patients With Breast Cancer
13 A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol. 2014 Jul;25(7):1333-9.