Details of the Drug Combination

General Information of Drug Combination (ID: DCKLHEQ)

• Drug Combination Name: Tamsulosin + Solifenacin
• Indication: LUTS; Status: Phase 1 [1]
• Component Drugs:
  Tamsulosin (DM5QF9V): Small molecular drug
  Solifenacin (DMG592Q): 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	[6]

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	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

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	[8]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[9]

Indication(s) of Solifenacin

Disease Entry	ICD 11	Status	REF
Overactive bladder	GC50.0	Approved	[4]
Priapism	N.A.	Investigative	[5]

Solifenacin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Antagonist	[10]

Solifenacin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Lower Urinary Tract Symptoms	DCDHYLX	N. A.	Phase 4	[12]

References

• [1] ClinicalTrials.gov (NCT02180997) Clinical Trial to Investigate the Pharmacokinetic Drug Interaction Between Solifenacin 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: 7483).
• [5] Solifenacin FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout ... Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6.
• [11] Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
• [12] ClinicalTrials.gov (NCT02715024) Study to Evaluate the Clinical Efficacy and Safety of Tamsulosin Alone or in Combination With Solifenacin for the Treatment in Men With Lower Urinary Tract Symptoms Including Overactive Bladder Symptoms