Details of the Drug Combination

General Information of Drug Combination (ID: DCSZYVH)

• Drug Combination Name: Framycetin + Rifaximin
• Indication: Constipation-predominant Irritable Bowel Syndrome; Status: Phase 1 [1]
• Component Drugs:
  Framycetin (DMF8DNE): Small molecular drug
  Rifaximin (DMW1TV2): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Framycetin

Disease Entry	ICD 11	Status	REF
Acute liver failure	DB91	Approved	[2]
Alcoholic cirrhosis of liver	DB94	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Blepharoconjunctivitis	N.A.	Approved	[4]
Corneal abrasion	NA06.4	Approved	[4]
Hepatic coma	N.A.	Approved	[4]
Hepatic encephalopathy	DB99.5	Approved	[4]
Keratitis	N.A.	Approved	[5]
Urinary tract infection	GC08	Approved	[6]
Uveitis	9A96.Z	Investigative	[4]

Framycetin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 16S ribosomal RNA (Bact 16S rRNA)	TT38DW5	NOUNIPROTAC	Binder	[9]
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[10]

Framycetin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[11]
Aminoglycoside N-acetyltransferase (aacC2)	DEJADS9	AAC6_ACIBA	Metabolism	[11]

Framycetin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Increases Expression	[12]
N-alpha-acetyltransferase 15, NatA auxiliary subunit (NAA15)	OT53SIZG	NAA15_HUMAN	Increases ADR	[13]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases ADR	[13]

Indication(s) of Rifaximin

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[7]
Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[8]
Hepatic encephalopathy	DB99.5	Approved	[8]

Rifaximin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]

Rifaximin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]

Rifaximin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[16]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[16]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[17]

References

• [1] ClinicalTrials.gov (NCT00945334) Neomycin and Rifaximin Plus Neomycin in Treating Methane Positive Constipation Predominant Irritable Bowel Syndrome
• [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: 709).
• [3] Drug information of Framycetin, 2008. eduDrugs.
• [4] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [5] Bacterial isolates, antimicrobial susceptibility, and clinical characteristics of bacterial keratitis in dogs presenting to referral practice in Australia. Vet Ophthalmol. 2016 Sep;19(5):418-26.
• [6] Prostatectomy and infection. J Urol. 1971 Dec;106(6):910-2.
• [7] ClinicalTrials.gov (NCT01654939) Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease. U.S. National Institutes of Health.
• [8] Rifaximin FDA Label
• [9] Antistaphylococcal activity of gentamicin. Minerva Med. 1975 Dec 8;66(84):4505-26.
• [10] Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin. Arch Microbiol. 2008 May;189(5):441-9.
• [11] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [12] A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals. Toxicology. 2009 Oct 1;264(1-2):1-9. doi: 10.1016/j.tox.2009.07.021. Epub 2009 Aug 7.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [14] Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability. AAPS J. 2017 May;19(3):806-813.
• [15] Probable interaction between warfarin and rifaximin in a patient treated for small intestine bacterial overgrowth. Ann Pharmacother. 2011 May;45(5):e25.
• [16] Solomonsterols A and B from Theonella swinhoeiThe first example of C-24 and C-23 sulfated sterols from a marine source endowed with a PXR agonistic activity. J Med Chem. 2011 Jan 13;54(1):401-5.
• [17] Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity. J Med Chem. 2011 Jul 14;54(13):4590-9. doi: 10.1021/jm200241s. Epub 2011 Jun 3.