Details of the Drug

General Information of Drug (ID: DMW1TV2)

Drug Name

Rifaximin

Synonyms

RCIFAX; Rifaximin (bioadhesive/ gastrointestinal extended release); Rifaximin (bioadhesive/ gastrointestinal extended release), Salix Pharmaceuticals

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

785.9

Topological Polar Surface Area (xlogp)

6.9

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

5

Hydrogen Bond Acceptor Count (hbondacc)

12

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [2]
Elimination: 0.035% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 6 hours [3]
Metabolism: The drug is metabolized via the hepatic [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 10.9065 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 0.001 mg/mL [2]

Chemical Identifiers

Formula: C43H51N3O11
IUPAC Name: [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.14,7.05,35.026,34.027,32]heptatriaconta-1(35),2,4,9,19,21,25(36),26(34),28,30,32-undecaen-13-yl] acetate
Canonical SMILES: C[C@H]1/C=C/C=C(\\C(=O)NC2=C(C3=C(C4=C(C(=C3O)C)O[C@@](C4=O)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C5=C2N6C=CC(=CC6=N5)C)O)/C
InChI: InChI=1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1
InChIKey: NZCRJKRKKOLAOJ-XRCRFVBUSA-N

Cross-matching ID

PubChem CID: 6436173
ChEBI ID: CHEBI:75246
CAS Number: 80621-81-4
DrugBank ID: DB01220
TTD ID: D04ITO
VARIDT ID: DR00073
INTEDE ID: DR1422
ACDINA ID: D00593

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Rifaximin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Midostaurin	DMI6E0R	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Midostaurin.	Acute myeloid leukaemia [2A60]	[24]
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Rifaximin due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[24]
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[25]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[26]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[27]
PF-04449913	DMSB068	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[24]
GS-5885	DMSL3DX	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by GS-5885.	Hepatitis virus infection [1E50-1E51]	[28]
Bempedoic acid	DM1CI9R	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Bempedoic acid.	Hyper-lipoproteinaemia [5C80]	[29]
Tolvaptan	DMIWFRL	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Tolvaptan.	Hypo-osmolality/hyponatraemia [5C72]	[25]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[30]
Ibrutinib	DMHZCPO	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Ibrutinib.	Mature B-cell lymphoma [2A85]	[24]
Nilotinib	DM7HXWT	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Nilotinib.	Myeloproliferative neoplasm [2A20]	[31]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[32]
Lonafarnib	DMGM2Z6	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Lonafarnib.	Premature ageing appearance [LD2B]	[33]
Enzalutamide	DMGL19D	Moderate	Accelerated clearance of Rifaximin due to the transporter induction by Enzalutamide.	Prostate cancer [2C82]	[34]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[24]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Rifaximin due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[35]
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⏷ Show the Full List of 17 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Edetate disodium	E00186	8759	Complexing agent
Eisenoxyd	E00585	56841934	Colorant
Glyceryl palmitostearate	E00396	114690	Coating agent; Diluent; Flavoring agent; Gelling agent; Modified-release agent; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Rifaximin 550 mg tablet	550 mg	Oral Tablet	Oral
Rifaximin 200 mg tablet	200 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	ClinicalTrials.gov (NCT01654939) Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease. U.S. National Institutes of Health.
2	BDDCS applied to over 900 drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	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.
7	Probable interaction between warfarin and rifaximin in a patient treated for small intestine bacterial overgrowth. Ann Pharmacother. 2011 May;45(5):e25.
8	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
9	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
10	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
11	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
12	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
13	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
14	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
15	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
16	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
17	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
18	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
19	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.
20	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
21	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
22	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
23	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
24	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
25	Cerner Multum, Inc. "Australian Product Information.".
26	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
27	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
28	Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
29	Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
30	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
31	Product Information. Tasigna (nilotinib). Novartis Pharmaceuticals, East Hanover, NJ.
32	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
33	Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
34	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
35	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.