Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C47H64N4O12.ClH |
Molecular Weight | 913.492 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 9 / 9 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C4=C(O)C(\C=N\N5CCN(CC5)C6CCCC6)=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)C(O)=C4C(O)=C3C
InChI
InChIKey=YAXMCEWRTZAGIM-DSTWUDMISA-N
InChI=1S/C47H64N4O12.ClH/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);1H/b13-12+,22-17+,25-14-,48-23+;/t24-,26+,27+,28+,33-,38-,39+,43+,47-;/m0./s1
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C47H64N4O12 |
Molecular Weight | 877.0307 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 9 / 9 |
E/Z Centers | 1 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170Curator'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
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2364672 Sources: http://www.drugbank.ca/drugs/DB01201 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | PRIFTIN Approved Useis 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 Date9.3934079E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 Sources: Page: p.1Discoloration urine 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 Co-administed with:: isoniazid, po(q.d.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
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%) Sources: Page: p.6ALT increased (0.28%) AST increased (0.28%) LDH increased (0.28%) Bilirubin increased (0.28%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
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.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
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.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
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.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
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.) Sources: Page: p.6pyrazinamide, po(q.d.) ethambutol, po(q.d.) |
unhealthy n = 361 Health Status: unhealthy Condition: Pulmonary tuberculosis caused by Mycobacterium tuberculosis Population Size: 361 Sources: Page: p.6 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
PubMed
Title | Date | PubMed |
---|---|---|
Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex. | 1987 |
|
In vitro properties of rifapentine (MDL473) relevant to its use in intermittent chemotherapy of tuberculosis. | 1987 Jun |
|
In vitro activity of new rifamycins against rifampicin-resistant M. tuberculosis and MAIS-complex mycobacteria. | 1987 Sep |
|
Bactericidal activity in vitro of various rifamycins against Mycobacterium avium and Mycobacterium tuberculosis. | 1990 Mar |
|
In vivo activities of newer rifamycin analogs against Mycobacterium avium infection. | 1991 Oct |
|
Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M. tuberculosis and their penetration into mouse peritoneal macrophages. | 1992 Jan |
|
Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. | 1993 Dec |
|
Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine. | 1993 Mar |
|
Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice. | 1994 Aug |
|
Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex. | 1994 Feb |
|
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model. | 1994 Nov |
|
Effectiveness of rifabutin alone or in combination with isoniazid in preventive therapy of mouse tuberculosis. | 1994 Oct |
|
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 |
|
New drugs for tuberculosis. | 1995 Sep |
|
Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophages. | 1995 Sep |
|
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis. | 1996 Dec |
|
How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice? | 1996 Feb |
|
Rifapentine is active in vitro and in vivo against Toxoplasma gondii. | 1996 Jun |
|
Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations. | 1996 Nov |
|
[In vitro anti-MAC activities of new quinolones in focus (1)]. | 1996 Sep |
|
Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. | 1997 May |
|
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. | 1998 Jul |
|
Development of rifapentine susceptibility tests for Mycobacterium tuberculosis. | 1999 Jan |
|
Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice. | 1999 Oct |
|
Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis. | 1999 Sep |
|
In vitro susceptibilities of rapidly growing mycobacteria to telithromycin (HMR 3647) and seven other antimicrobials. | 2000 Jan |
|
Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens. | 2000 May |
|
Comparison of the in vitro activities of rifapentine and rifampicin against Mycobacterium tuberculosis complex. | 2000 Oct |
|
Activity of rifapentine and its metabolite 25-O-desacetylrifapentine compared with rifampicin and rifabutin against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M. bovis BCG. | 2000 Oct |
|
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. | 2006 Oct |
|
Structure and anti-TB activity of trachylobanes from the liverwort Jungermannia exsertifolia ssp. cordifolia. | 2010 Apr 23 |
|
Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. | 2011 Dec 1 |
|
Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. | 2011 Sep 15 |
|
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. | 2013 Nov |
|
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015 Jun |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170
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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/3116733
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
Edited
Sat Dec 16 11:31:53 UTC 2023
by
admin
on
Sat Dec 16 11:31:53 UTC 2023
|
Record UNII |
5915QBW8LA
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DTXSID60860763
Created by
admin on Sat Dec 16 11:31:53 UTC 2023 , Edited by admin on Sat Dec 16 11:31:53 UTC 2023
|
PRIMARY | |||
|
DBSALT002329
Created by
admin on Sat Dec 16 11:31:53 UTC 2023 , Edited by admin on Sat Dec 16 11:31:53 UTC 2023
|
PRIMARY | |||
|
127923-87-9
Created by
admin on Sat Dec 16 11:31:53 UTC 2023 , Edited by admin on Sat Dec 16 11:31:53 UTC 2023
|
PRIMARY | |||
|
135565704
Created by
admin on Sat Dec 16 11:31:53 UTC 2023 , Edited by admin on Sat Dec 16 11:31:53 UTC 2023
|
PRIMARY | |||
|
5915QBW8LA
Created by
admin on Sat Dec 16 11:31:53 UTC 2023 , Edited by admin on Sat Dec 16 11:31:53 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
PARENT -> SALT/SOLVATE |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |