Details of the Drug Combination

General Information of Drug Combination (ID: DCO099B)

• Drug Combination Name: Tadalafil + Finasteride
• Indication: Benign Prostatic Hyperplasia; Status: Phase 1 [1]
• Component Drugs:
  Tadalafil (DMJZHT1): Small molecular drug
  Finasteride (DMWV3TZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tadalafil

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[2]
Erectile dysfunction	HA01.1	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[2]
Pulmonary hypertension	BB01	Approved	[2]
Priapism	N.A.	Investigative	[2]

Tadalafil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Inhibitor	[6]

Tadalafil 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]

Tadalafil Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]

Tadalafil Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)	OTT8Q1AP	PDE5A_HUMAN	Decreases Activity	[9]

Indication(s) of Finasteride

Disease Entry	ICD 11	Status	REF
Baldness, male pattern	N.A.	Approved	[4]
Benign prostatic hyperplasia	GA90	Approved	[5]
Retinopathy	9B71	Approved	[4]

Finasteride Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Oxo-5-alpha-steroid 4-dehydrogenase (SRD5A)	TT2A0DR	S5A1_HUMAN; S5A2_HUMAN; PORED_HUMAN	Inhibitor	[10]
Steroid 5-alpha-reductase 2 (SRD5A2)	TTT02K8	S5A2_HUMAN	Inhibitor	[11]

Finasteride Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[13]

Finasteride Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Decreases Activity	[14]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[15]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)	OTTG0NFD	S5A2_HUMAN	Decreases Activity	[16]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[17]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Response To Substance	[19]

References

• [1] ClinicalTrials.gov (NCT01139762) A Study of Tadalafil Use With Finasteride in Men With Enlarged Prostates and Urinary Symptoms
• [2] Tadalafil 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: 7299).
• [4] Finasteride FDA Label
• [5] 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: 6818).
• [6] Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
• [7] In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319.
• [8] Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65.
• [9] Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety. Expert Opin Drug Saf. 2005 May;4(3):531-40. doi: 10.1517/14740338.4.3.531.
• [10] The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [13] Drug Interactions Flockhart Table
• [14] Inhibition of the activity of 'basic' 5 alpha-reductase (type 1) detected in DU 145 cells and expressed in insect cells. J Steroid Biochem Mol Biol. 1994 Mar;48(4):347-52.
• [15] Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer. Cancer Res. 2000 Dec 1;60(23):6630-40.
• [16] Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicol In Vitro. 2007 Apr;21(3):502-8.
• [17] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [18] Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
• [19] Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009 May 20;29(20):6449-60. doi: 10.1523/JNEUROSCI.0708-09.2009.