Details of the Drug Combination

General Information of Drug Combination (ID: DC6IVT1)

• Drug Combination Name: Esomeprazole + Levofloxacin
• Indication: Helicobacter Pylori Infection; Status: Phase 1 [1]
• Component Drugs:
  Esomeprazole (DM7BN0X): Small molecular drug
  Levofloxacin (DMS60RB): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Esomeprazole

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Approved	[2]
Gastrinoma	2C10.1	Approved	[2]
Laryngeal disorder	N.A.	Approved	[2]
Nausea	MD90	Approved	[2]
Peptic esophagitis	N.A.	Approved	[2]
Peptic ulcer	DA61	Approved	[3]

Esomeprazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gastric H(+)/K(+) ATPase (Proton pump)	TTLOKXP	ATP4A_HUMAN; ATP4B_HUMAN	Modulator	[6]

Esomeprazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[7]

Esomeprazole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[8]

Indication(s) of Levofloxacin

Disease Entry	ICD 11	Status	REF
Acute maxillary sinusitis	N.A.	Approved	[4]
Anthrax	1B97	Approved	[4]
Bacterial infection	1A00-1C4Z	Approved	[5]
Latent tuberculosis infection	N.A.	Approved	[4]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[4]
Pyelonephritis	N.A.	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[4]
Staphylococcus aureus infection	N.A.	Approved	[4]
Streptococcal pneumonia	N.A.	Approved	[4]
Pneumonia caused by chlamydia	N.A.	Investigative	[4]

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	[9]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[10]

Levofloxacin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[11]

Levofloxacin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Activity	[12]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[13]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[13]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[13]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[13]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[13]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[13]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[13]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[13]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[14]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Helicobacter Pylori Infection	DCPJ5KC	N. A.	Phase 4	[15]
Helicobacter Pylori Infection	DC5OPJP	N. A.	Phase 1	[1]

References

• [1] ClinicalTrials.gov (NCT02596620) Levofloxacin-containing Therapies In Second Line Helicobacter Pylori Eradication
• [2] Esomeprazole 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: 5488).
• [4] Levofloxacin FDA Label
• [5] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Predictive performance of physiologically based pharmacokinetic (PBPK) modeling of drugs extensively metabolized by major cytochrome P450s in children. Clin Pharmacol Ther. 2018 Jul;104(1):188-200.
• [8] The effects of drugs with immunosuppressive or immunomodulatory activities on xenobiotics-metabolizing enzymes expression in primary human hepatocytes. Toxicol In Vitro. 2015 Aug;29(5):1088-99.
• [9] 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.
• [10] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [11] 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.
• [12] Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. 2015 Mar;29(3):135-9.
• [13] 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.
• [14] 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.
• [15] ClinicalTrials.gov (NCT04432233) Intravenous Triple Therapy in the Treatment of Helicobacter Pylori Infection and Related Complications Caused by Active Peptic Ulcer Disease