Details of the Drug Combination

General Information of Drug Combination (ID: DCE5ENS)

Drug Combination Name
Bedaquiline Rifapentine
Indication
Disease Entry Status REF
Tuberculosis Phase 1 [1]
Component Drugs Bedaquiline   DM3906J Rifapentine   DMCHV4I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Bedaquiline
Disease Entry ICD 11 Status REF
Drug-resistant tuberculosis N.A. Approved [2]
Multi-drug resistant tuberculosis MG52.00 Approved [3]
Pulmonary tuberculosis 1B10.Z Approved [2]
Bedaquiline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mycobacterium Proton pump (MycB Prop) TT19K0L A0A1Q4HQH4_9MYCO Modulator [7]
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Bedaquiline Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Indication(s) of Rifapentine
Disease Entry ICD 11 Status REF
Pulmonary tuberculosis 1B10.Z Approved [4]
Tuberculosis 1B10-1B1Z Approved [5]
Macular degeneration 9B78.3 Investigative [6]
Rifapentine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA-directed RNA polymerase (RNAP) TTHKJLN NOUNIPROTAC Binder [9]
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Rifapentine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Rifapentine Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [12]
Arylacetamide deacetylase (AADAC) OT8VACT2 AAAD_HUMAN Decreases Acetylation [13]
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References

1 ClinicalTrials.gov (NCT02216331) PK Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects (TMC207-CL002)
2 Bedaquiline FDA Label
3 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
4 Rifapentine FDA Label
5 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
6 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
8 Bedaquiline metabolism: enzymes and novel metabolites. Drug Metab Dispos. 2014 May;42(5):863-6.
9 Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998 Jul;42(7):1853-7.
10 Inhibitory potential of twenty five anti-tuberculosis drugs on CYP activities in human liver microsomes. Biol Pharm Bull. 2015;38(9):1425-9.
11 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
12 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
13 Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. Biochem Pharmacol. 2011 Dec 1;82(11):1747-56.