Details of the Drug Combination

General Information of Drug Combination (ID: DCAYQZN)

Drug Combination Name

Darexaban maleate Ketoconazole

Indication

Disease Entry	Status	REF
Pharmacokinetics of Darexaban and Metabolites	Phase 1	[1]

Component Drugs

Darexaban maleate DMC40SD

Ketoconazole DMPZI3Q

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Darexaban maleate

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Discontinued in Phase 3	[2]

Darexaban maleate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[5]
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Indication(s) of Ketoconazole

Disease Entry	ICD 11	Status	REF
Blastomycosis	1F22	Approved	[3]
Chromomycosis	N.A.	Approved	[3]
Coccidioidomycosis	1F25	Approved	[3]
Cutaneous candidiasis	1F23.14	Approved	[3]
Fungal infection	1F29-1F2F	Approved	[4]
Histoplasmosis	N.A.	Approved	[3]
Invasive candidiasis	1F23	Approved	[3]
Mycoses	1F2Z	Approved	[3]
Oral candidiasis	1F23.0	Approved	[3]
Paracoccidioidomycosis	N.A.	Approved	[3]
Pityriasis simplex	N.A.	Approved	[3]
Prostate adenocarcinoma	N.A.	Approved	[3]
Tinea corporis	1F28.Y	Approved	[3]
Tinea cruris	1F28.3	Approved	[3]
Tinea versicolor	1F2D.0	Approved	[3]
Tinea pedis	1F28.2	Investigative	[3]

Ketoconazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Inhibitor	[6]
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Ketoconazole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
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Ketoconazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
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Ketoconazole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases ADR	[9]
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References

1	ClinicalTrials.gov (NCT01405989) To Evaluate if Multiple Doses of Ketoconazole Change the Blood Concentration of YM150 (Darexaban)
2	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020726)
3	Ketoconazole 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: 2568).
5	The pharmacokinetics of darexaban are not affected to a clinically relevant degree by rifampicin, a strong inducer of P-glycoprotein and CYP3A4. Br J Clin Pharmacol. 2013 Feb;75(2):440-9.
6	Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
7	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
8	The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59.
9	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.