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(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=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
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 Date1999 |
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 |
|
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model. | 1994 Nov |
|
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 |
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 17:32:18 GMT 2023
by
admin
on
Sat Dec 16 17:32:18 GMT 2023
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Record UNII |
XJM390A33U
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Record Status |
Validated (UNII)
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Record Version |
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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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262-743-9
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2378
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135403821
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CHEMBL1660
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Related Record | Type | Details | ||
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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
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METABOLIC ENZYME -> INDUCER | |||
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EXCRETED UNCHANGED |
FECAL
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> INDUCER | |||
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EXCRETED UNCHANGED |
URINE
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
FECAL
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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