Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0895)
Drug Name
Itraconazole
Synonyms
Itraconazol; Itraconazol [Spanish]; Itraconazolum [Latin]; Itralek; Itrizole; Oriconazole; Orungal; Prokanazol; R-51211; SUBA Itraconazole; Sempera; Spherazole; Spherazole CR; Spherazole IR; Sporal; Sporamelt; Sporanox; Sporonox; Traconal; Triasporin; Canadiol; Candistat; Canditral; Hyphanox; cis-Itraconazole; itraconazole; (+-)-1-sec-Butyl-4-(p-(4-(p-(((2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-1-piperazinyl)phenyl)-delta(sup 2)-1,2,4-triazolin-5-one; BRN 6042047; Itrac
Indication Blastomycosis [ICD11: 1F22] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 705.6 Topological Polar Surface Area 101
Heavy Atom Count 49 Rotatable Bond Count 11
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 9
Cross-matching ID
PubChem CID
6917738
PubChem SID
12012955 ; 14839906 ; 23950781 ; 43529166 ; 57371668 ; 80687815 ; 114786875 ; 129477277 ; 138818153 ; 143350865 ; 226641989
ChEBI ID
ChEBI:6076
CAS Number
84625-61-6
TTD Drug ID
D0V4IB
Formula
C35H38Cl2N8O4
Canonical SMILES
CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5COC(O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl
InChI
1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m1/s1
InChIKey
VHVPQPYKVGDNFY-AVQIMAJZSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Hydroxyitraconazole DM001039
108222
Oxidation - O-Demethylation 1 [5] , [6] , [7] , [8] , [9]
Keto-itraconazole DM001040
53865186
Unclear 1 [5] , [6]
N-desalkyl-itraconazole DM001041
53789808
Oxidation - N-Dealkylation 1 [5] , [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001277 Itraconazole Hydroxyitraconazole Oxidation - O-Demethylation CYP3A4 [5], [6], [7], [8], [9]
MR001278 Itraconazole Keto-itraconazole Unclear Unclear [5], [6]
MR001279 Itraconazole N-desalkyl-itraconazole Oxidation - N-Dealkylation Unclear [5], [6]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[3]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1355 Akkermansia muciniphila Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1394 Blautia luti Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1404 Clostridium sporogenes Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [4]
⏷ Show the Full List of 9  DME(s)
References
1 Itraconazole was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone. Ther Drug Monit. 2006 Feb;28(1):73-5.
3 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.
4 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
5 Role of itraconazole metabolites in CYP3A4 inhibition. Drug Metab Dispos. 2004 Oct;32(10):1121-31.
6 Accurate prediction of dose-dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data Clin Pharmacol Ther. 2010 Oct;88(4):499-505. doi: 10.1038/clpt.2010.119.
7 Repurposing antifungals: population pharmacokinetics of itraconazole and hydroxy-itraconazole following administration of a nanocrystal formulation. J Antimicrob Chemother. 2023 May 3;78(5):1219-1224. doi: 10.1093/jac/dkad072.
8 Does metabolite matter? Defining target itraconazole and hydroxy-itraconazole serum concentrations for blastomycosis. Mycoses. 2023 May;66(5):412-419. doi: 10.1111/myc.13565.
9 Influence of Gender, Body Mass Index, and Age on the Pharmacokinetics of Itraconazole in Healthy Subjects: Non-Compartmental Versus Compartmental Analysis. Front Pharmacol. 2022 Jun 15;13:796336. doi: 10.3389/fphar.2022.796336.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.