Details of the Drug Combination

General Information of Drug Combination (ID: DC2TBRF)

Drug Combination Name
Itraconazole Risdiplam
Indication
Disease Entry Status REF
Spinal Muscular Atrophy Phase 1 [1]
Component Drugs Itraconazole   DMCR1MV Risdiplam   DMIMF8J
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Itraconazole
Disease Entry ICD 11 Status REF
Aspergillosis 1F20 Approved [2]
Blastomycosis 1F22 Approved [2]
Fungal infection 1F29-1F2F Approved [3]
Fusariosis N.A. Approved [2]
Histoplasmosis N.A. Approved [2]
Invasive candidiasis 1F23 Approved [2]
Mycoses 1F2Z Approved [2]
Candidemia 1F23.3Y Investigative [2]
Esophageal candidiasis N.A. Investigative [2]
Itraconazole Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hedgehog signaling pathway (HS pathway) TT4LXBC NOUNIPROTAC Inhibitor [5]
Candida Cytochrome P450 51 (Candi ERG11) TTTSOUD CP51_CANAL Modulator [6]
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Itraconazole Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Itraconazole Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [9]
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Itraconazole Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [10]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [11]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Decreases Activity [12]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [13]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [16]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [16]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Decreases Activity [17]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Response To Substance [18]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Risdiplam
Disease Entry ICD 11 Status REF
Spinal muscular atrophy 8B61 Approved [4]
Risdiplam Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [19]
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References

1 ClinicalTrials.gov (NCT02633709) A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) Given by Mouth in Healthy Volunteers
2 Itraconazole FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076104.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
8 Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone. Ther Drug Monit. 2006 Feb;28(1):73-5.
9 Investigation into UDP-glucuronosyltransferase (UGT) enzyme kinetics of imidazole- and triazole-containing antifungal drugs in human liver microsomes and recombinant UGT enzymes. Drug Metab Dispos. 2010 Jun;38(6):923-9.
10 Itraconazole cis-diastereoisomers activate aryl hydrocarbon receptor AhR and pregnane X receptor PXR and induce CYP1A1 in human cell lines and human hepatocytes. Toxicology. 2017 May 15;383:40-49.
11 Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
12 The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
13 Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci. 2007 May;97(1):32-43.
14 Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48.
15 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
16 Anti-mycotics suppress interleukin-4 and interleukin-5 production in anti-CD3 plus anti-CD28-stimulated T cells from patients with atopic dermatitis. J Invest Dermatol. 2001 Dec;117(6):1635-46. doi: 10.1046/j.0022-202x.2001.01566.x.
17 Inhibition of 11-hydroxysteroid dehydrogenase 2 by the fungicides itraconazole and posaconazole. Biochem Pharmacol. 2017 Apr 15;130:93-103. doi: 10.1016/j.bcp.2017.01.010. Epub 2017 Jan 25.
18 Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homolo... Antimicrob Agents Chemother. 2008 Oct;52(10):3597-603.
19 A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br J Clin Pharmacol. 2019 Jan;85(1):181-193.