Details of the Drug Combination

General Information of Drug Combination (ID: DCZ94TJ)

• Drug Combination Name: Avanafil + Ketoconazole
• Indication: Erectile Dysfunction; Status: Phase 1 [1]
• Component Drugs:
  Avanafil (DM75CXN): Small molecular drug
  Ketoconazole (DMPZI3Q): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Avanafil

Disease Entry	ICD 11	Status	REF
Erectile dysfunction	HA01.1	Approved	[2]

Avanafil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Modulator	[5]

Avanafil Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]

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	[7]

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	[8]

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	[9]

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	[10]

References

• [1] ClinicalTrials.gov (NCT00770042) To Evaluate The Effect Of Ketoconazole, Ritonavir and Erythromycin on the Safety and Pharmacokinetics of Avanafil
• [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: 7448).
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. Expert Opin Pharmacother. 2013 Jul;14(10):1333-44.
• [7] Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
• [8] 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.
• [9] 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.
• [10] 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.