Details of the Drug Combination

General Information of Drug Combination (ID: DCWWHMP)

• Drug Combination Name: Celecoxib + Oseltamivir
• Indication: Influenza, Human; Status: Phase 3 [1]
• Component Drugs:
  Celecoxib (DM6LOQU): Small molecular drug
  Oseltamivir (DMGO72P): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Celecoxib

Disease Entry	ICD 11	Status	REF
Dysmenorrhea	GA34.3	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Osteoarthritis	FA00-FA05	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Pain	MG30-MG3Z	Phase 3	[3]
Colon cancer	2B90.Z	Investigative	[2]
Familial adenomatous polyposis	2B90.Y	Investigative	[2]
Precancerous condition	N.A.	Investigative	[2]

Celecoxib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[7]

Celecoxib Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[11]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[12]

Indication(s) of Oseltamivir

Disease Entry	ICD 11	Status	REF
Influenza	1E30-1E32	Approved	[4]
Influenza virus infection	1E30-1E32	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]

Oseltamivir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Influenza Neuraminidase (Influ NA)	TT50QJ3	NRAM_I33A0	Inhibitor	[13]

Oseltamivir Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[15]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[16]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[17]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[17]

Oseltamivir Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[18]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Increases Metabolism	[19]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Response To Substance	[20]

References

• [1] ClinicalTrials.gov (NCT02108366) Treatment of Severe Influenza A Infection
• [2] Celecoxib FDA Label
• [3] 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: 2892).
• [4] Oseltamivir FDA Label
• [5] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [6] ClinicalTrials.gov (NCT04261270) A Randomized,Open,Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia
• [7] Pfizer. Product Development Pipeline. March 31 2009.
• [8] Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther. 2000 May;293(2):453-9.
• [9] Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus. Aquat Toxicol. 2007 Mar 10;81(3):286-92.
• [10] Celecoxib is a substrate of CYP2D6: impact on celecoxib metabolism in individuals with CYP2C9*3 variants. Drug Metab Pharmacokinet. 2018 Oct;33(5):219-227.
• [11] Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics. 2009 Sep;10(9):1489-510.
• [12] Drug interactions in dentistry: the importance of knowing your CYPs. J Am Dent Assoc. 2004 Mar;135(3):298-311.
• [13] Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.
• [14] Nonclinical pharmacokinetics of oseltamivir and oseltamivir carboxylate in the central nervous system. Antimicrob Agents Chemother. 2009 Nov;53(11):4753-61.
• [15] Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21.
• [16] Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81.
• [17] FDA Drug Development and Drug Interactions
• [18] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [19] In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones. Chem Biol Interact. 2022 Apr 25;357:109883. doi: 10.1016/j.cbi.2022.109883. Epub 2022 Mar 9.
• [20] Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and oseltamivir by suppressing the expression of carboxylesterases HCE1 and HCE2. Mol Pharmacol. 2007 Sep;72(3):686-94. doi: 10.1124/mol.107.036889. Epub 2007 May 30.