Details of the Drug Combination

General Information of Drug Combination (ID: DCRN6VE)

• Drug Combination Name: Tamsulosin + Mirabegron
• Indication: Cardiovascular; Status: Phase 1 [1]
• Component Drugs:
  Tamsulosin (DM5QF9V): Small molecular drug
  Mirabegron (DMS1GYT): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tamsulosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[2]
Urinary retention	MF50.3	Approved	[3]

Tamsulosin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Modulator	[5]

Tamsulosin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]

Tamsulosin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[7]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[8]

Indication(s) of Mirabegron

Disease Entry	ICD 11	Status	REF
Overactive bladder	GC50.0	Approved	[4]

Mirabegron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-3 (ADRB3)	TTMXGCW	ADRB3_HUMAN	Modulator	[9]

Mirabegron Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Nephrolithiasis	DCY82ZV	N. A.	Phase 4	[11]
Overactive Bladder	DCWAMR7	N. A.	Phase 4	[12]

References

• [1] ClinicalTrials.gov (NCT01489696) A Study to Evaluate Cardiovascular Interactions Between Mirabegron and Tamsulosin
• [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: 488).
• [3] Tamsulosin 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: 7445).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes. Xenobiotica. 1998 Oct;28(10):909-22.
• [7] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [8] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [9] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [10] Role of cytochrome p450 isoenzymes 3A and 2D6 in the in vivo metabolism of mirabegron, a beta-3-adrenoceptor agonist. Clin Drug Investig. 2013 Jun;33(6):429-40.
• [11] ClinicalTrials.gov (NCT02095665) Ureteral Stent-related Pain and Mirabegron (SPAM) Trial
• [12] ClinicalTrials.gov (NCT02656173) A Phase 4 Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Male Subjects With Overactive Bladder (OAB) Symptoms, While Taking the Alpha Blocker for Benign Prostatic Hypertrophy (BPH)