Details of the Drug Combination

General Information of Drug Combination (ID: DC695L1)

• Drug Combination Name: Rabeprazole + Levofloxacin
• Indication: Helicobacter Pylori Infection; Status: Phase 4 [1]
• Component Drugs:
  Rabeprazole (DMMZXIW): Small molecular drug
  Levofloxacin (DMS60RB): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Rabeprazole

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Gastrinoma	2C10.1	Approved	[3]
Peptic ulcer	DA61	Approved	[3]

Rabeprazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gastric H(+)/K(+) ATPase alpha (ATP4A)	TTF1QVM	ATP4A_HUMAN	Inhibitor	[6]

Rabeprazole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]

Rabeprazole Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[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	[9]
Staphylococcus Topoisomerase IV (Stap-coc parC)	TTIXTO3	PARC_STAAS	Modulator	[9]

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	[10]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[11]

Levofloxacin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[12]

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	[13]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[14]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[14]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[14]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[14]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[14]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[14]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[14]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[15]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[14]

References

• [1] ClinicalTrials.gov (NCT05023577) Antibiotic Combination for H. Pylori Eradication in Penicillin-allergic Patients
• [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: 7290).
• [3] Rabeprazole FDA Label
• [4] Levofloxacin FDA Label
• [5] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [6] Review article: rabeprazole's tolerability profile in clinical trials. Aliment Pharmacol Ther. 1999 Oct;13 Suppl 5:17-23.
• [7] Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9.
• [8] Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes. Eur J Clin Pharmacol. 2006 Aug;62(8):597-603.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] 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.
• [11] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.