General Information of Drug Combination (ID: DCKOGVI)

Drug Combination Name
Esomeprazole Metronidazole
Indication
Disease Entry Status REF
Helicobacter Pylori Infection Phase 4 [1]
Component Drugs Esomeprazole   DM7BN0X Metronidazole   DMTIVEN
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [8]
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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 [9]
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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 [10]
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Indication(s) of Metronidazole
Disease Entry ICD 11 Status REF
Abscess N.A. Approved [4]
Amoebiasis 1A36 Approved [5]
Anaerobic bacteria infectious disease N.A. Approved [4]
Bacteremia 1A73 Approved [4]
Bacterial vaginosis MF3A Approved [4]
Bladder squamous cell carcinoma N.A. Approved [4]
Endometritis N.A. Approved [4]
Liver abscess (disease) N.A. Approved [4]
Peritonitis N.A. Approved [4]
Trichomoniasis N.A. Approved [4]
Crohn disease DD70 Phase 3 [6]
Perianal crohn disease DD70.4 Phase 3 [7]
Giardiasis N.A. Investigative [4]
Metronidazole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Deoxyribonucleic acid (Bact DNA) TTS1W4A NOUNIPROTAC Modulator [11]
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Metronidazole Interacts with 14 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [13]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [14]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [14]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [14]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [15]
Nitroreductase (NTR) DE8R7QY A0A482G3K9_GIAIN Metabolism [16]
Nitroreductase (NTR) DE2VSMT A2DZ34_TRIVA Metabolism [16]
Nitroreductase (NTR) DEQGIMN A4K8Z3_ENTHI Metabolism [16]
Nitroreductase (NTR) DEP7ECA B1R7B9_CLOPF Metabolism [17]
Nitroreductase (NTR) DEAN5EW NFSB_ENTCL Metabolism [18]
Nitroreductase (NTR) DE3U2Y6 A0A377KR04_ENTCA Metabolism [19]
Nitroreductase (NTR) DEUW4J0 A0A376H6M5_ENTGA Metabolism [19]
Nitroreductase (NTR) DELAPDY A0A1C0X0J8_BACFG Metabolism [20]
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⏷ Show the Full List of 14 DME(s)
Metronidazole Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [21]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) OTRGGIFP DRB1_HUMAN Affects Expression [22]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Affects Expression [22]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [21]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Helicobacter Pylori Infection DCM2TO6 N. A. Phase 4 [23]
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References

1 ClinicalTrials.gov (NCT03557437) High Dose of Amoxicillin and Metronidazole Plus Bismuth For Helicobacter Pylori Treatment
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 Metronidazole FDA Label
5 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018517.
6 ClinicalTrials.gov (NCT00509639) Evaluation of Topical 10% Metronidazole Ointment for the Treatment of Active Perianal Crohn's Disease. U.S. National Institutes of Health.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 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.
10 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.
11 DNA breakage due to metronidazole treatment. Mutat Res. 2001 Jul 1;478(1-2):153-8.
12 Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? Ann Pharmacother. 2007 Apr;41(4):653-8.
13 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
14 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases). Antimicrob Agents Chemother. 2009 Feb;53(2):458-64.
17 Acetamide--a metabolite of metronidazole formed by the intestinal flora. Biochem Pharmacol. 1979 Dec 15;28(24):3611-5.
18 Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
19 Mechanism of metronidazole-resistance by isolates of nitroreductase-producing Enterococcus gallinarum and Enterococcus casseliflavus from the human intestinal tract. FEMS Microbiol Lett. 2003 Aug 29;225(2):195-200.
20 Isolation of metronidazole-resistant Bacteroides fragilis carrying the nimA nitroreductase gene from a patient in Washington State. J Clin Microbiol. 2004 Sep;42(9):4127-9. Case Reports
21 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.
22 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
23 ClinicalTrials.gov (NCT04024527) High Dose of Dual Therapy Plus Metronidazole for Helicobacter Pylori RescueTreatment