RIFABUTIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C46H62N4O11
Molecular Weight	847.0047
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(=O)C(NC(=O)C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)=C5NC6(CCN(CC(C)C)CC6)N=C5C4=C3C2=O

InChI

InChIKey=ATEBXHFBFRCZMA-VXTBVIBXSA-N

InChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12+,20-15+,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C46H62N4O11
Molecular Weight	847.0047
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050689s022lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/cdi/rifabutin.html http://www.rxlist.com/mycobutin-drug.htm http://www.wikidoc.org/index.php/Rifabutin

Rifabutin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. It is FDA approved for the prophylaxis of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. Multiple dosing of rifabutin has been associated with induction of hepatic metabolic enzymes of the CYP3A subfamily. Rifabutin’s predominant metabolite (25-desacetyl rifabutin: LM565), may also contribute to this effect. Similarly, concomitant medications that competitively inhibit the CYP3A activity may increase plasma concentrations of rifabutin. Common adverse reactions include discoloration of skin, rash, diarrhea, disorder of taste, indigestion, loss of appetite, nausea, vomiting, increased liver aminotransferase level (mild), ocular discoloration, uveitis, abnormal color of body fluid.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18713760	Substrate 661
DNA-directed RNA polymerase subunit beta 5 Target ID: P0A8V2 Gene ID: 948488.0 Gene Symbol: rpoB Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15805525 \| https://www.ncbi.nlm.nih.gov/pubmed/7849340	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Disseminated Mycobacterium avium complex (MAC) disease 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050689s022lbl.pdf	Preventing		Approved 8583	MYCOBUTIN Approved Use MYCOBUTIN Capsules are indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. Launch Date 1992

C_max

Value	Dose	Co-administered	Analyte	Population
691 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
613 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9287 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5803 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
45 h REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
58 h REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
21.5% REVIEW https://pubmed.ncbi.nlm.nih.gov/8785251/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFABUTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050689Orig1s018lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050689Orig1s018lbl.pdf	Other AEs: Abdominal pain, Asthenia... Other AEs: Abdominal pain (4%) Asthenia (1%) Chest pain (1%) Fever (2%) Headache (3%) Pain (1%) Anorexia (2%) Diarrhea (3%) Dyspepsia (3%) Eructation (3%) Flatulence (2%) Nausea (6%) Nausea and vomiting (3%) Vomiting (1%) Myalgia (2%) Insomnia (1%) Rash (11%) Taste perversion (3%) Urine discoloration (30%) Alkaline phosphatase increased (<1%) SGOT increased (7%) SGPT increased (9%) Anemia (6%) Eosinophilia (1%) Leukopenia (17%) Neutropenia (25%) Thrombocytopenia (5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050689Orig1s018lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inducer 1087 substrate 1946	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP3A 227 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 UGT1A1 246 UGT1A4 98 UGT1A6 136 UGT1A9 148 UGT2B7 197 UGT2B15 84	AADAC 1	P-gp 301 OATP1B1 29 OATP1B3 8 MRP2 146

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
UGT1A4 100	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	likely
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	no
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	no
MRP2 625	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/24060875/	no
OATP1B1 1095	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/24060875/	no
UGT1A6 171	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	no
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	no
CYP3A 317	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely [IC50 31.5 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
UGT1A1 303	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
UGT2B15 84	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28663285/	unlikely
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/24060875/	yes
OATP1B3 970	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/24060875/	yes
P-gp 1932	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/24060875/	yes
CYP3A4 2633	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/10418969/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050689s016lbl.pdf	yes	yes (co-administration study) Comment: many DDIs: see https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050689s016lbl.pdf#page=3 Sources: https://pubmed.ncbi.nlm.nih.gov/10418969/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050689s016lbl.pdf

Drug as victim

Target	Modality	Activity	Metabolite
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9145845/	no
AADAC 1	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21856291/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9145845/	yes	25-O-DEACETYLRIFABUTIN 1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:45367	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45367
ChemicalBook	CB0702764	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0702764
eMolecules	29541954	https://www.emolecules.com/cgi-bin/more?vid=29541954
eMolecules	3717994	https://www.emolecules.com/cgi-bin/more?vid=3717994
Selleck Chemicals	Rifabutin(Mycobutin)	http://www.selleckchem.com/products/Rifabutin(Mycobutin).html
ZINC	ZINC000169621215	http://zinc15.docking.org/substances/ZINC000169621215

PubMed

Title	Date	PubMed
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis.	1998-07	9661035
[Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental murine tuberculosis: (1). A study on the efficacy of short course treatment with the intratracheal and intravenous infection model].	1998-02	9545697
Rapid drug susceptibility of Mycobacterium avium complex using a fluorescence quenching method.	1997-08	9269603
Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents.	1997-05	9164417
Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.	1997-05	9145860
New ophthalmic manifestations of presumed rifabutin-related uveitis.	1997-04	9101573
Clinically used antimicrobial drugs against experimental pneumocystosis, singly and in combination: analysis of drug interactions and efficacies.	1997-02	9021174
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.	1996-12	9124846
Evaluation of the activities of rifabutin combined with atovaquone or low-dose of cotrimoxazole for prevention of pneumocystosis and toxoplasmosis in a dual infection rat model.	1996-09-01	8822822
Comparative activity of azithromycin against clinical isolates of mycobacteria.	1996-09	8889727
In vitro and in vivo effects of rifabutin alone or combined with atovaquone against Toxoplasma gondii.	1996-09	8878573
Susceptibility testing of Mycobacterium avium complex isolates.	1996-08	8843278
Rifapentine is active in vitro and in vivo against Toxoplasma gondii.	1996-06	8725996
Use of rifabutin in combination with atovaquone, clindamycin, pyrimethamine, or sulfadiazine for treatment of toxoplasmic encephalitis in mice.	1996-05	8793398
Chemotherapeutic activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium tuberculosis in C57BL/6 mice.	1996-04	8762850
Activity of rifabutin, clarithromycin, ethambutol, sparfloxacin and amikacin, alone and in combination, against Mycobacterium avium complex in human macrophages.	1996-03	9182107
How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?	1996-02	8834894
Rifamycin resistance in mycobacteria.	1996-01-01	8761722
In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.	1995-10	8619585
Activity of seven antimicrobial agents, alone and in combination, against AIDS-associated isolates of Mycobacterium avium complex.	1995-09	8830013
New drugs for tuberculosis.	1995-09	8590571
In-vitro and intracellular activity of rifabutin on drug-susceptible and multiple drug-resistant (MDR) tubercle bacilli.	1995-08	8522465
[Extra and intracellular activity of dirithromycin against Mycobacterium avium].	1995-04	7567116
Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model.	1995-03	7793895
Comparison of activities of fluoroquinolones in murine macrophages infected with Mycobacterium tuberculosis.	1995-03	7793885
Mutation position and type of substitution in the beta-subunit of the RNA polymerase influence in-vitro activity of rifamycins in rifampicin-resistant Mycobacterium tuberculosis.	1995-02	7759399
Clinical experience with rifabutin in the treatment of mycobacterial infections.	1995	8867175
A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions.	1994-11	7872747
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model.	1994-11	7872741
[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review].	1994-11	7837725
In vitro model to assess effect of antimicrobial agents on Encephalitozoon cuniculi.	1994-10	7840584
Activity of KRM-1648, a new benzoxazinorifamycin, against Mycobacterium tuberculosis in a murine model.	1994-10	7840552
Rifabutin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy.	1994-06	7521834
Rifabutin and sparfloxacin but not azithromycin inhibit binding of Mycobacterium avium complex to HT-29 intestinal mucosal cells.	1994-05	8067766
In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.	1994-05	8067748
Rifabutin is active in murine models of toxoplasmosis.	1994-03	8203856
Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex.	1994-02	8192449
Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice.	1993-12	8256897
Anti-Mycobacterium avium activity of quinolones: in vitro activities.	1993-09	8239587
Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.	1993-03	8384809
Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.	1993-01	8448815
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.	1993-01	8431020
In vitro susceptibility of Mycobacterium avium complex to antibacterial agents.	1987-11	3440370
Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods.	1985-10	4073881
Comparative in vitro activities of MDL 473, rifampin, and ansamycin against Mycobacterium intracellulare.	1985-09	4073865
Determination of in vitro susceptibility of mycobacteria to ansamycin.	1985-09	3929660
Activity of the spiropiperidyl rifamycin LM 427 on rifampicin resistant Mycobacterium tuberculosis.	1984-09-01	6100178
LM 427, a new spiropiperidylrifamycin: in vitro and in vivo studies.	1983-11	6317622
In vitro susceptibility of Mycobacterium avium complex and Mycobacterium tuberculosis strains to a spiro-piperidyl rifamycin.	1982-09	6289711
Biological activity of a new class of rifamycins. Spiro-piperidyl-rifamycins.	1980-10	6256335

Patents

Sample Use Guides

In Vivo Use Guide

It is recommended that Rifabutin Capsules be administered at a dose of 300 mg once daily. For those patients with propensity to nausea, vomiting, or other gastrointestinal upset, administration of Rifabutin at doses of 150 mg twice daily taken with food may be useful.

Route of Administration: Oral

In Vitro Use Guide

The IC50 of rifabutin was 26.5 mg/L in a different series of experiments using an enzyme-linked immunoassay and the T. gondii high virulence strain.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:28:33 GMT 2025` Edited by `admin` on `Mon Mar 31 18:28:33 GMT 2025`
Record UNII	1W306TDA6S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RIFABUTIN

Official Name

English

TALICIA COMPONENT RIFABUTIN

Preferred Name

English

LM-427

Code

English

RIFABUTIN [VANDF]

Common Name

English

LM 427

Code

English

RIFABUTIN [ORANGE BOOK]

Common Name

English

MYCOBUTIN

Code

English

RIFABUTIN [USP-RS]

Common Name

English

ANSAMYCIN

Common Name

English

RIFABUTIN [JAN]

Common Name

English

RIFABUTIN [EP MONOGRAPH]

Common Name

English

RIFABUTIN [MI]

Common Name

English

1',4-DIDEHYDRO-1-DEOXY-1,4-DIHYDRO-5'-(2-METHYLPROPYL)-1-OXORIFAMYCIN XIV

Common Name

English

rifabutin [INN]

Common Name

English

Rifabutin [WHO-DD]

Common Name

English

4-DEOXO-3,4-(2-SPIRO-(N-ISOBUTYL-4-PIPERIDYL))-(1H)-IMIDAZO-(2,5-DIHYDRO)RIFAMYCIN S

Common Name

English

RIFABUTIN [USAN]

Common Name

English

4-N-ISOBUTYLSPIROPIPERIDYLRIFAMYCIN S

Common Name

English

RIFABUTIN [HSDB]

Common Name

English

RIFABUTIN [USP MONOGRAPH]

Common Name

English

RIFABUTIN [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ04AB04