U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C47H64N4O12
Molecular Weight 877.0325
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of RIFAPENTINE

SMILES

C[C@@]1([H])/C(/[H])=C(\[H])/C(/[H])=C(/C)\C(=Nc2c(/C(/[H])=N/N3CCN(CC3)C4CCCC4)c(c5c(c(c(C)c6c5C(=O)[C@@](C)(O/C(/[H])=C(\[H])/[C@@]([H])([C@@]([H])(C)[C@]([H])([C@]([H])(C)[C@@]([H])([C@]([H])(C)[C@@]1([H])O)O)OC(=O)C)OC)O6)O)c2O)O)O

InChI

InChIKey=WDZCUPBHRAEYDL-GZAUEHORSA-N
InChI=1S/C47H64N4O12/c1-24-13-12-14-25(2)46(59)49-37-32(23-48-51-20-18-50(19-21-51)31-15-10-11-16-31)41(56)34-35(42(37)57)40(55)29(6)44-36(34)45(58)47(8,63-44)61-22-17-33(60-9)26(3)43(62-30(7)52)28(5)39(54)27(4)38(24)53/h12-14,17,22-24,26-28,31,33,38-39,43,53-57H,10-11,15-16,18-21H2,1-9H3,(H,49,59)/b13-12+,22-17+,25-14-,48-23+/t24-,26+,27+,28+,33-,38-,39+,43+,47-/m0/s1

HIDE SMILES / InChI

Molecular Formula C47H64N4O12
Molecular Weight 877.0325
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 9 / 9
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/21024lbl.pdf http://www.drugbank.ca/drugs/DB01201

PRIFTIN® (rifapentine) is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. PRIFTIN must always be used in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible. Rifapentine 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. And it acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death. 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. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency. Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
PRIFTIN

Approved Use

is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. PRIFTIN must always be used in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible

Launch Date

9.3934079E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25.8 μg/mL
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ISONIAZID
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
15.05 μg/mL
600 mg 1 times / 3 days steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
817 μg × h/mL
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ISONIAZID
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
319.54 μg × h/mL
600 mg 1 times / 3 days steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16.6 h
900 mg single, oral
dose: 900 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ISONIAZID
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
13.19 h
600 mg 1 times / 3 days steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2.3%
600 mg 1 times / 3 days steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RIFAPENTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg/kg 1 times / day multiple, oral
MTD
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources: Page: p.2, p.4
healthy
n = 6
Health Status: healthy
Sex: M+F
Population Size: 6
Sources: Page: p.2, p.4
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Sources: Page: p.1
Disc. AE: Hepatotoxicity...
Other AEs: Hyperbilirubinemia, Discoloration urine...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity
Other AEs:
Hyperbilirubinemia
Discoloration urine
Clostridium difficile colitis
Sources: Page: p.1
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
Disc. AE: Hepatitis, ALT increased...
AEs leading to
discontinuation/dose reduction:
Hepatitis (0.28%)
ALT increased (0.28%)
AST increased (0.28%)
LDH increased (0.28%)
Bilirubin increased (0.28%)
Sources: Page: p.6
AEs

AEs

AESignificanceDosePopulation
Clostridium difficile colitis
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Sources: Page: p.1
Discoloration urine
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Sources: Page: p.1
Hyperbilirubinemia
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Sources: Page: p.1
Hepatotoxicity Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Sources: Page: p.1
ALT increased 0.28%
Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
AST increased 0.28%
Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
Bilirubin increased 0.28%
Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
Hepatitis 0.28%
Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
LDH increased 0.28%
Disc. AE
600 mg 2 times / week multiple, oral
Recommended
Dose: 600 mg, 2 times / week
Route: oral
Route: multiple
Dose: 600 mg, 2 times / week
Co-administed with::
isoniazid, po(q.d.)
pyrazinamide, po(q.d.)
ethambutol, po(q.d.)
Sources: Page: p.6
unhealthy
n = 361
Health Status: unhealthy
Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis
Population Size: 361
Sources: Page: p.6
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 230 uM]
yes [IC50 357 uM]
yes [IC50 70 uM]
yes
yes
yes
yes
yes
yes
yes
PubMed

PubMed

TitleDatePubMed
Comparison of the sensitivity of mycobacteria to the cyclopentyl rifamycin DL473 and rifampicin.
1982 Aug
Comparative in vitro activities of MDL 473, rifampin, and ansamycin against Mycobacterium intracellulare.
1985 Sep
In vitro activities against mycobacteria of two long-acting rifamycins, FCE22807 and CGP40/469A (SPA-S-565).
1990 Jun
Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.
1991 Jul
In vivo activities of newer rifamycin analogs against Mycobacterium avium infection.
1991 Oct
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model.
1994 Nov
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 Feb
Development of rifapentine susceptibility tests for Mycobacterium tuberculosis.
1999 Jan
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: PRIFTIN should be administered at a dose of 600 mg twice weekly for two months as directly observed therapy (DOT), with an interval of no less than 3 consecutive days (72 hours) between doses, in combination with other anti- tuberculosis drugs as part of an appropriate regimen which includes daily companion drugs such as isoniazid (INH), ethambutol (EMB) and pyrazinamide (PZA).
600 mg twice weekly for two months
Route of Administration: Oral
In Vitro Use Guide
In a comparison of in vitro properties of rifapentine (RIF), the minimal inhibitory concentration of RIF against Mycobacterium tuberculosis in Tween-albumin liquid medium was usually 0.02 micrograms/ml; the bactericidal activity against a log phase culture was slightly less than that of RMP and the recovery after pulsed exposures to 1 microgram/ml of RIF lasting 6, 24 and 96 h was identical for the two rifamycins.
Substance Class Chemical
Created
by admin
on Sat Jun 26 01:01:38 UTC 2021
Edited
by admin
on Sat Jun 26 01:01:38 UTC 2021
Record UNII
XJM390A33U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIFAPENTINE
INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
KTC-1
Code English
RIFAPENTINE [VANDF]
Common Name English
R-773
Code English
DL-473
Code English
R-77-3
Code English
RIFAPENTINE [INN]
Common Name English
RIFAPENTINE [MART.]
Common Name English
RIFAMYCIN AF/ACPP
Common Name English
MDL 473
Code English
RIFAPENTINE [MI]
Common Name English
3-((4-CYCLOPENTYL-1-PIPERAZINYL)IMINO)METHYL)RIFAMYCIN
Common Name English
RIFAMYCIN, 3-(((4-CYCLOPENTYL-1-PIPERAZINYL)IMINO)METHYL)-
Common Name English
3-(((4-CYCLOPENTYL-1-PIPERAZINYL)IMINO)METHYL)RIFAMYCIN
Common Name English
RIFAPENTIN
Common Name English
RIFAPENTINE [ORANGE BOOK]
Common Name English
RIFAPENTINE [WHO-DD]
Common Name English
PRIFITIN
Brand Name English
PRIFTIN
Brand Name English
ANTIBIOTIC DL-473IT
Code English
RIFAPENTINE [USAN]
Common Name English
MDL-473
Code English
3-(N-(4-CYCLOPENTYL-1-PIPERAZINYL)FORMIMIDOYL)RIFAMYCIN
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C280
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
NDF-RT N0000007911
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
FDA ORPHAN DRUG 89495
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
NDF-RT N0000007911
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
NDF-RT N0000007911
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
WHO-VATC QJ04AB05
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
NDF-RT N0000175501
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
FDA ORPHAN DRUG 89695
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
LIVERTOX 846
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
EU-Orphan Drug EU/3/10/750
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
FDA ORPHAN DRUG 89595
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
WHO-ATC J04AB05
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
NDF-RT N0000007911
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
Code System Code Type Description
EVMPD
SUB10311MIG
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
MERCK INDEX
M9614
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C66516
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
WIKIPEDIA
Rifapentine
Created by admin on Sat Jun 26 01:01:39 UTC 2021 , Edited by admin on Sat Jun 26 01:01:39 UTC 2021
PRIMARY
FDA UNII
XJM390A33U
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
DRUG BANK
DB01201
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
INN
4765
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
LACTMED
Rifapentine
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
EPA CompTox
61379-65-5
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
RXCUI
35617
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY RxNorm
CAS
61379-65-5
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
ECHA (EC/EINECS)
262-743-9
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
DRUG CENTRAL
2378
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
PUBCHEM
135403821
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
ChEMBL
CHEMBL1660
Created by admin on Sat Jun 26 01:01:38 UTC 2021 , Edited by admin on Sat Jun 26 01:01:38 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
The bound concentration increased slightly (,2%) as the concentration of 14C-rifapentine increased from 0.5 to 10 mg/ml. At concentrations above 10 mg/ml, protein binding did not appear to vary with increasing concentration.
BINDING
METABOLIC ENZYME -> INDUCER
EXCRETED UNCHANGED
FECAL
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INDUCER
EXCRETED UNCHANGED
URINE
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
FECAL
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION