Details of the Drug Combination

General Information of Drug Combination (ID: DC6DRHP)

• Drug Combination Name: Nitrofurantoin + Cefuroxime
• Indication: Complication of Surgical Procedure; Status: Phase 1 [1]
• Component Drugs:
  Nitrofurantoin (DM7PQIK): Small molecular drug
  Cefuroxime (DMSIMD8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Nitrofurantoin

Disease Entry	ICD 11	Status	REF
Urinary tract infection	GC08	Approved	[2]

Nitrofurantoin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Deoxyribonucleic acid (Bact DNA)	TTS1W4A	NOUNIPROTAC	Breaker	[5]

Nitrofurantoin 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	[6]

Nitrofurantoin Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Metabolism	[7]
Nitroreductase (NTR)	DEAVXGM	A0A412R9E4_9FIRM	Metabolism	[8]
NADPH-dependent oxidoreductase (nfrA)	DE82GV7	NRFA_STAA8	Metabolism	[9]
NADPH-dependent nitroreductase (nfrA1)	DE21PLI	NFRA1_BACSU	Metabolism	[10]
Nitroreductase (NTR)	DE7XBKW	A0A174SJF2_9CLOT	Metabolism	[8]
Nitroreductase (NTR)	DEP7ECA	B1R7B9_CLOPF	Metabolism	[8]
Nitroreductase (NTR)	DEH3ABM	A0A351QTB1_CLOSP	Metabolism	[8]
Nitroreductase (NTR)	DE3U2Y6	A0A377KR04_ENTCA	Metabolism	[11]
Nitroreductase (NTR)	DEUW4J0	A0A376H6M5_ENTGA	Metabolism	[11]
Nitroreductase (NTR)	DE5LYXF	A0A2X3BKF5_CLOSG	Metabolism	[12]

Nitrofurantoin Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Transport	[13]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[14]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[15]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[16]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[17]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[18]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Response To Substance	[19]

Indication(s) of Cefuroxime

Disease Entry	ICD 11	Status	REF
Acute bronchiolitis	N.A.	Approved	[3]
Acute bronchitis	CA42	Approved	[4]
Acute gonococcal cervicitis	N.A.	Approved	[3]
Acute maxillary sinusitis	N.A.	Approved	[3]
Acute otitis media	AB00	Approved	[3]
Bacteremia	1A73	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[3]
Staphylococcus aureus infection	N.A.	Approved	[3]
Sinusitis	CA0A.Z	Investigative	[3]

Cefuroxime Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[20]

Cefuroxime Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[21]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[21]

References

• [1] ClinicalTrials.gov (NCT02789579) The Preventive Infection Role of One Week Antibiotics Before Minimally Invasive Upper Tract Lithotomy
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009175.
• [3] Cefuroxime FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] On the nature of the adaptive response induced by mitomycin C in Vibrio cholerae OGAWA 154 cells. Biochem Biophys Res Commun. 1996 Mar 27;220(3):509-14.
• [6] The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol. 2005 May;67(5):1758-64.
• [7] Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
• [8] Isolation of nitrofurantoin-resistant mutants of nitroreductase-producing Clostridium sp. strains from the human intestinal tract. Antimicrob Agents Chemother. 1998 May;42(5):1121-6.
• [9] Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev. 2008 May;32(3):474-500.
• [10] Conversion of NfsA, the major Escherichia coli nitroreductase, to a flavin reductase with an activity similar to that of Frp, a flavin reductase in Vibrio harveyi, by a single amino acid substitution. J Bacteriol. 1998 Jan;180(2):422-5.
• [11] 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.
• [12] Biotransformation of 1-nitropyrene in intestinal anaerobic bacteria. Microbiol Immunol. 1982;26(11):993-1005.
• [13] Effects of the flavonoid chrysin on nitrofurantoin pharmacokinetics in rats: potential involvement of ABCG2. Drug Metab Dispos. 2007 Feb;35(2):268-74.
• [14] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [15] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
• [16] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [17] Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes. Cell Biol Toxicol. 2022 Oct;38(5):847-864. doi: 10.1007/s10565-021-09610-3. Epub 2021 May 22.
• [18] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
• [19] Roles of DT diaphorase in the genotoxicity of nitroaromatic compounds in human and fish cell lines. J Toxicol Environ Health. 1997 Oct 10;52(2):137-48. doi: 10.1080/00984109708984057.
• [20] Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI. J Antimicrob Chemother. 2003 Mar;51(3):523-30.
• [21] 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.