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targets (1) enzymes (7)
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Identification
Name Rifapentine
Accession Number DB01201 (APRD01217)
Type small molecule
Groups approved
Description

Rifapentine is an antibiotic drug used in the treatment of tuberculosis. It inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Cyclopentyl rifampin
Synonyms
Cyclopentyl rifampin
Salts Not Available
Brand names
Name Company
Priftin
Brand mixtures Not Available
Categories
  • Leprostatic Agents
  • Antimycobacterials
  • Antibiotics, Antitubercular
CAS number 61379-65-5
Weight Average: 877.0307
Monoisotopic: 876.452073532
Chemical Formula C47H64N4O12
InChI Key InChIKey=WDZCUPBHRAEYDL-GZAUEHORSA-N
InChI
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
Plain Text
IUPAC Name
(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-26-[(E)-N-(4-cyclopentylpiperazin-1-yl)carboximidoyl]-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1,3,5(28),9,19,21,25(29),26-octaen-13-yl acetate
SMILES
CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(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\N1CCN(CC1)C1CCCC1)=C2O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Ansamycins
  • Lactams
Substructures
  • Ansamycins
  • Carboxylic Acids and Derivatives
  • Benzofurans
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetates
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Ethers
  • Phenylpropenes
  • Piperazines
  • Benzene and Derivatives
  • Methoxyphenols
  • Enamines
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Hydrazine Derivatives
  • Lactams
  • Benzoyl Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
  • Ketones
Pharmacology
Indication For the treatment of pulmonary tuberculosis.
Pharmacodynamics 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. 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.
Mechanism of action Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
Absorption Rapidly and well absorbed from the gastrointestinal tract.
Volume of distribution
  • 70.2 ± 9.1 L
Protein binding 97.7% (bound to plasma proteins)
Metabolism Hepatic
Route of elimination Following a single 600 mg oral dose of radiolabeled rifapentine to healthy volunteers (n=4), 87% of the total 14C rifapentine was recovered in the urine (17%) and feces (70%).
Half life Not Available
Clearance
  • Apparent Oral cl=2.51 +/- 0.14 L/h [Male tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol]
  • Apparent Oral cl=1.69 +/- 0.41 L/h [Female tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol]
Toxicity Not Available
Affected organisms
  • Mycobacterium
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Priftin 150 mg tablet 3.96 USD tablet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 4 PhysProp
Predicted Properties
Property Value Source
water solubility 2.13e-02 g/l ALOGPS
logP 4.83 ALOGPS
logP 3.56 ChemAxon Molconvert
logS -4.6 ALOGPS
pKa 8.65 ChemAxon Molconvert
hydrogen acceptor count 14 ChemAxon Molconvert
hydrogen donor count 6 ChemAxon Molconvert
polar surface area 220.15 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 242 ChemAxon Molconvert
polarizability 93.14 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00879 Link_out
KEGG Compound C08059 Link_out
PubChem Compound 6323497 Link_out
PubChem Substance 46507322 Link_out
ChemSpider 4883449 Link_out
ChEBI 8861 Link_out
ChEMBL 8861 Link_out
Therapeutic Targets Database DAP000426 Link_out
PharmGKB PA10180 Link_out
HET RPT Link_out
RxList http://www.rxlist.com/cgi/generic/priftin.htm Link_out
Drugs.com http://www.drugs.com/cdi/rifapentine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Rifapentine Link_out
ATC Codes
  • J04AB05
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (1.74 MB)
MSDS show (58.3 KB)
Interactions
Drug Interactions
Drug Interaction
Bromazepam Rifapentine may decrease the serum concentration of bromazepam by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if rifapentine is initiated, discontinued or dose changed.
Erlotinib Decreased levels/effect of erlotinib
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Methadone The rifamycin decreases the effect of methadone
Norethindrone This product may cause a slight decrease of contraceptive effect
Telithromycin Rifapentine may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Rifapentine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Terbinafine Rifapentine may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.
Tipranavir Concomitant therapy may cause decreased Tipranavir and increased Rifapentine plasma concentrations.
Tramadol Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inducer, Rifapentine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifapentine is initiated, discontinued or dose changed.
Tretinoin The strong CYP2C8 inducer, Rifapentine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rifapentine is initiated, discontinued or dose changed.
Verapamil Rifapentine, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifapentine is initiated, discontinued or dose changed.
Voriconazole Rifapentine may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifapentin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.
Zidovudine Rifapentin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifapentin is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. DNA-directed RNA polymerase beta' chain

Pharmacological action: yes
Actions: inhibitor

DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates

Organism class: bacterial
UniProt ID: P0A674 Link_out
Gene: rpoC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Williams DL, Spring L, Collins L, Miller LP, Heifets LB, Gangadharam PR, Gillis TP: Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998 Jul;42(7):1853-7. Pubmed
  4. Tupin A, Gualtieri M, Roquet-Baneres F, Morichaud Z, Brodolin K, Leonetti JP: Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns. Int J Antimicrob Agents. 2010 Jun;35(6):519-23. Epub 2010 Feb 24. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C8

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Actions: inducer

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 3A43

Actions: inducer

Exhibits low testosterone 6-beta-hydroxylase activity

UniProt ID: Q9HB55 Link_out
Gene: CYP3A43 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 3A5

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A7

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:46