Details of the Drug Combination

General Information of Drug Combination (ID: DCFQPL3)

• Drug Combination Name: Levofloxacin + Pantoprazole
• Indication: Melatonin Deficiency; Status: Phase 1 [1]
• Component Drugs:
  Levofloxacin (DMS60RB): Small molecular drug
  Pantoprazole (DMSVOCZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levofloxacin

Disease Entry	ICD 11	Status	REF
Acute maxillary sinusitis	N.A.	Approved	[2]
Anthrax	1B97	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Latent tuberculosis infection	N.A.	Approved	[2]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[2]
Pyelonephritis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
Streptococcal pneumonia	N.A.	Approved	[2]
Pneumonia caused by chlamydia	N.A.	Investigative	[2]

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 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Activity	[10]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[11]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[11]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[11]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[11]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[11]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[11]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[11]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[12]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[11]

Indication(s) of Pantoprazole

Disease Entry	ICD 11	Status	REF
Gastrinoma	2C10.1	Approved	[4]
Gastroesophageal reflux disease	DA22.Z	Approved	[5]
Peptic ulcer	DA61	Approved	[4]

Pantoprazole 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]

Pantoprazole Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]

Pantoprazole Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[16]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[15]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[17]

Pantoprazole Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[18]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Increases Expression	[19]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Helicobacter Pylori Infection	DCXGPBT	N. A.	Phase 4	[20]

References

• [1] ClinicalTrials.gov (NCT04352062) Melatonin Supplementation in Postmenopausal Women With H. Pylori-associated Dyspepsia
• [2] Levofloxacin FDA Label
• [3] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [4] Pantoprazole 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: 7260).
• [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] 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.
• [11] 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.
• [12] 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.
• [13] A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
• [14] Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11.
• [15] Interaction of proton pump inhibitors with cytochromes P450: consequences for drug interactions. Yale J Biol Med. 1996 May-Jun;69(3):203-9.
• [16] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [17] Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):447-460.
• [18] Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist. Biochem Pharmacol. 2010 May 1;79(9):1310-6. doi: 10.1016/j.bcp.2009.12.018. Epub 2010 Jan 8.
• [19] Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020 Jan;318:86-91. doi: 10.1016/j.toxlet.2019.10.016. Epub 2019 Oct 24.
• [20] ClinicalTrials.gov (NCT02466919) Study of Levofloxacin-based Concomitant Therapy for H. Pylori Eradication in Diabetic Patients