Details of the Drug Combination

General Information of Drug Combination (ID: DCCZT3O)

• Drug Combination Name: Apixaban + DU-176b
• Indication: Atrial Fibrillation; Status: Phase 1 [1]
• Component Drugs:
  Apixaban (DM89JLN): Small molecular drug
  DU-176b (DMCIJBH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Apixaban

Disease Entry	ICD 11	Status	REF
Thrombosis	DB61-GB90	Approved	[2]

Apixaban Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[4]

Apixaban Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[6]

Apixaban Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

Indication(s) of DU-176b

Disease Entry	ICD 11	Status	REF
Atrial fibrillation	BC81.3	Approved	[3]

DU-176b Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Modulator	[10]

DU-176b Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

DU-176b Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Aortic Stenosis	DCQGYWA	N. A.	Phase 3	[13]

References

• [1] ClinicalTrials.gov (NCT05262322) Study to Evaluate the Use of Direct Oral Anticoagulants in UK Clinical Practice For Patients With a First Stroke Attributable to Nonvalvular Atrial Fibrillation
• [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: 6390).
• [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: 7575).
• [4] Pfizer. Product Development Pipeline. March 31 2009.
• [5] Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa. Am J Cardiovasc Drugs. 2016 Apr;16(2):119-27.
• [6] Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013 Apr;41(4):827-35.
• [7] In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010 Mar;38(3):448-58.
• [8] Apixaban. Hosp Pharm. 2013 Jun;48(6):494-509.
• [9] Apixaban. After hip or knee replacement: LMWH remains the standard treatment. Prescrire Int. 2012 Sep;21(130):201-2, 204.
• [10] 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. (Target id: 2359).
• [11] Edoxaban drug-drug interactions with ketoconazole, erythromycin, and cyclosporine. Br J Clin Pharmacol. 2016 Dec;82(6):1591-1600.
• [12] Edoxaban drug-drug interactions with ketoconazole, erythromycin, and cyclosporine. Br J Clin Pharmacol. 2016 Dec;82(6):1591-1600.
• [13] ClinicalTrials.gov (NCT05035277) AntiCoagulation Versus AcetylSalicylic Acid After Transcatheter Aortic Valve Implantation