Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C47H64N4O12 |
| Molecular Weight | 877.0307 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 9 / 9 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
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)C(\C=N\N5CCN(CC5)C6CCCC6)=C(O)C4=C3C2=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
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 Date1999 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
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: |
healthy |
|
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: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hepatotoxicity... Other AEs: Hyperbilirubinemia, Discoloration urine... AEs leading to discontinuation/dose reduction: Hepatotoxicity Other AEs:Hyperbilirubinemia Sources: Discoloration 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hepatitis, ALT increased... AEs leading to discontinuation/dose reduction: Hepatitis (0.28%) Sources: ALT 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: |
unhealthy Health Status: unhealthy Sources: |
|
| 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: |
unhealthy Health Status: unhealthy Sources: |
|
| 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: |
unhealthy Health Status: unhealthy Sources: |
|
| 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: |
unhealthy Health Status: unhealthy Sources: |
| 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
| 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
| 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
| 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
| 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
PubMed
| Title | Date | PubMed |
|---|---|---|
| Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015-06 |
|
| A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. | 2013-11 |
|
| Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. | 2011-12-01 |
|
| Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. | 2011-09-15 |
|
| Structure and anti-TB activity of trachylobanes from the liverwort Jungermannia exsertifolia ssp. cordifolia. | 2010-04-23 |
|
| Potent in vitro antifungal activities of naturally occurring acetylenic acids. | 2008-07 |
|
| Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. | 2006-10 |
|
| Activities of moxifloxacin alone and in combination with other antimicrobial agents against multidrug-resistant Mycobacterium tuberculosis infection in BALB/c mice. | 2003-01 |
|
| Effectiveness of once-weekly rifapentine and moxifloxacin regimens against Mycobacterium tuberculosis in mice. | 2001-12 |
|
| Comparison of the in vitro activities of rifapentine and rifampicin against Mycobacterium tuberculosis complex. | 2000-10 |
|
| 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. | 2000-10 |
|
| Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens. | 2000-05 |
|
| In vitro susceptibilities of rapidly growing mycobacteria to telithromycin (HMR 3647) and seven other antimicrobials. | 2000-01 |
|
| Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice. | 1999-10 |
|
| Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis. | 1999-09 |
|
| Development of rifapentine susceptibility tests for Mycobacterium tuberculosis. | 1999-01 |
|
| Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. | 1998-07 |
|
| Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. | 1997-05 |
|
| Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis. | 1996-12 |
|
| Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations. | 1996-11 |
|
| [In vitro anti-MAC activities of new quinolones in focus (1)]. | 1996-09 |
|
| Rifapentine is active in vitro and in vivo against Toxoplasma gondii. | 1996-06 |
|
| How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice? | 1996-02 |
|
| New drugs for tuberculosis. | 1995-09 |
|
| Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophages. | 1995-09 |
|
| 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 |
|
| Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model. | 1994-11 |
|
| Effectiveness of rifabutin alone or in combination with isoniazid in preventive therapy of mouse tuberculosis. | 1994-10 |
|
| Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice. | 1994-08 |
|
| Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex. | 1994-02 |
|
| Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. | 1993-12 |
|
| Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine. | 1993-03 |
|
| Activity of rifapentine against Mycobacterium avium infection in beige mice. | 1992-05 |
|
| Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M. tuberculosis and their penetration into mouse peritoneal macrophages. | 1992-01 |
|
| In vivo activities of newer rifamycin analogs against Mycobacterium avium infection. | 1991-10 |
|
| Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages. | 1991-07 |
|
| In vitro activities against mycobacteria of two long-acting rifamycins, FCE22807 and CGP40/469A (SPA-S-565). | 1990-06 |
|
| Bactericidal activity in vitro of various rifamycins against Mycobacterium avium and Mycobacterium tuberculosis. | 1990-03 |
|
| New antibacterial drugs for the treatment of mycobacterial disease in man. | 1988-07 |
|
| In vitro activity of new rifamycins against rifampicin-resistant M. tuberculosis and MAIS-complex mycobacteria. | 1987-09 |
|
| In vitro properties of rifapentine (MDL473) relevant to its use in intermittent chemotherapy of tuberculosis. | 1987-06 |
|
| Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex. | 1987 |
|
| [In-vitro antimycobacterial activity of rifapentine (comparison with rifampicin)]. | 1986-12 |
|
| Comparative in vitro activities of MDL 473, rifampin, and ansamycin against Mycobacterium intracellulare. | 1985-09 |
|
| Comparison of the sensitivity of mycobacteria to the cyclopentyl rifamycin DL473 and rifampicin. | 1982-08 |
|
| Antibacterial activity of DL 473, a new semisynthetic rifamycin derivative. | 1981-08 |
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.
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| Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C280
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NDF-RT |
N0000007911
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FDA ORPHAN DRUG |
89495
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NDF-RT |
N0000007911
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NDF-RT |
N0000007911
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WHO-VATC |
QJ04AB05
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NDF-RT |
N0000175501
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FDA ORPHAN DRUG |
89695
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LIVERTOX |
NBK548547
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EU-Orphan Drug |
EU/3/10/750
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FDA ORPHAN DRUG |
89595
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WHO-ATC |
J04AB05
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NDF-RT |
N0000007911
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SUB10311MIG
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100000080562
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m9614
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C66516
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Rifapentine
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XJM390A33U
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DB01201
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XJM390A33U
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4765
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Rifapentine
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45304
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DTXSID8041115
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35617
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X-15
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61379-65-5
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CHEMBL1660
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)