Details of the Drug Combination

General Information of Drug Combination (ID: DCWNAK7)

• Drug Combination Name: Vibegron + Levofloxacin
• Indication: Overactive Bladder; Status: Phase 1 [1]
• Component Drugs:
  Vibegron (DMFR201): N.A.
  Levofloxacin (DMS60RB): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vibegron

Disease Entry	ICD 11	Status	REF
Overactive bladder	GC50.0	Approved	[2]

Vibegron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-3 (ADRB3)	TTMXGCW	ADRB3_HUMAN	Agonist	[2]

Vibegron Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Indication(s) of Levofloxacin

Disease Entry	ICD 11	Status	REF
Acute maxillary sinusitis	N.A.	Approved	[3]
Anthrax	1B97	Approved	[3]
Bacterial infection	1A00-1C4Z	Approved	[4]
Latent tuberculosis infection	N.A.	Approved	[3]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[3]
Pyelonephritis	N.A.	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[3]
Staphylococcus aureus infection	N.A.	Approved	[3]
Streptococcal pneumonia	N.A.	Approved	[3]
Pneumonia caused by chlamydia	N.A.	Investigative	[3]

Levofloxacin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial DNA gyrase (Bact gyrase)	TTN6J5F	GYRA_STAAU; GYRB_STAAU	Modulator	[6]
Staphylococcus Topoisomerase IV (Stap-coc parC)	TTIXTO3	PARC_STAAS	Modulator	[6]

Levofloxacin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[8]

Levofloxacin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[9]

Levofloxacin Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[10]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[10]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[11]

References

• [1] ClinicalTrials.gov (NCT01500382) A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [3] Levofloxacin FDA Label
• [4] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [5] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [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] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [9] Analysis of the drug-resistant characteristics of Klebsiella pneumoniae isolated from the respiratory tract and CTX-M ESBL genes. Genet Mol Res. 2015 Oct 5;14(4):12043-8.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.