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

General Information of Drug (ID: DR1073)
Drug Name
Metronidazole
Synonyms
Metronidaz; Metronidazol; Metronidazolo; Mexibol; Monagyl; Monasin; Novonidazol; Orvagil; Sanatrichom; Takimetol; Trichazol; Trichex; Trichocide; Trichomol; Trichopol; Tricocet; Tricom; Trikacide; Trikamon; Trikojol; Trikozol; Trimeks; Acromona; Anagiardil; Arilin; Atrivyl; Danizol; Deflamon; Efloran; Elyzol; Entizol; Flagemona; Flagesol; Flagil; Flagyl; Giatricol; Gineflavir; Meronidal; MetroGel; Trivazol; Vagilen; Vagimid; Vertisal; Wagitran; metronidazole; 2-Methyl-5-nitroimidazole-1-ethanol; 443-48-1; Bexon; Clont; Eumin; Klion; Klont; Nalox
Indication Amebiasis [ICD11: 1A36] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 171.15 Topological Polar Surface Area 83.9
Heavy Atom Count 12 Rotatable Bond Count 2
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
4173
PubChem SID
9412 ; 102189 ; 113379 ; 603052 ; 855672 ; 929590 ; 3138895 ; 4904671 ; 7481998 ; 7735852 ; 7847475 ; 7885193 ; 7979979 ; 8149429 ; 8152613 ; 10321393 ; 10523004 ; 10590514 ; 11112343 ; 11335182 ; 11360421 ; 11363929 ; 11366491 ; 11369053 ; 11371631 ; 11373698 ; 11377215 ; 11380270 ; 11447858 ; 11461393 ; 11466109 ; 11467229 ; 11484402 ; 11485677 ; 11488699 ; 11490322 ; 11491875 ; 11494849 ; 14748179 ; 17389815 ; 24870198 ; 24896667 ; 24896871 ; 24897314 ; 26611824 ; 26679371 ; 26683761 ; 26719631 ; 26746949 ; 26746950
ChEBI ID
ChEBI:6909
CAS Number
443-48-1
TTD Drug ID
D0A2ZX
Formula
C6H9N3O3
Canonical SMILES
CC1=NC=C(N1CCO)[N+](=O)[O-]
InChI
1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3
InChIKey
VAOCPAMSLUNLGC-UHFFFAOYSA-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
1-acetic acid-2-methyl DM004403
15249
Oxidation - Oxidationn 1 [12] , [13]
2-carboxylic DM004406
3028801
Oxidation - Oxidationn 1 [13]
2-hydroxymethyl DM004402 N. A. Oxidation - Oxidationn 1 [13]
2-hydroxymetronidazole DM004401
121858
Oxidation - Hydrolyzationn 1 [2] , [12] , [14] , [13]
5-amino DM004408
134701
Reduction - Reduction 1 [13]
Acetamide DM004400
178
Reduction - Reduction 1 [13]
Metronidazole Metabolite XI DM004404 N. A. Oxidation - Oxidationn 1 [13]
Metronidazole Metabolite XII DM004405 N. A. Oxidation - Oxidationn 1 [13]
Metronidazole Metabolite XIII DM004407 N. A. Oxidation - Oxidationn 1 [13]
N-(2-hydroxyethyl)-oxamic acid DM004399
165301
Reduction - Reduction 1 [13]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004725 Metronidazole N-(2-hydroxyethyl)-oxamic acid Reduction - Reduction Unclear [13]
MR004726 Metronidazole Acetamide Reduction - Reduction Unclear [13]
MR004727 Metronidazole 2-hydroxymetronidazole Oxidation - Hydrolyzationn CYP3A4 ... [2], [12], [14], [13]
MR004728 Metronidazole 2-hydroxymethyl Oxidation - Oxidationn Unclear [13]
MR004729 Metronidazole 1-acetic acid-2-methyl Oxidation - Oxidationn Unclear [12], [13]
MR004730 Metronidazole Metronidazole Metabolite XI Oxidation - Oxidationn Unclear [13]
MR004731 Metronidazole Metronidazole Metabolite XII Oxidation - Oxidationn Unclear [13]
MR004732 Metronidazole 2-carboxylic Oxidation - Oxidationn Unclear [13]
MR004733 Metronidazole Metronidazole Metabolite XIII Oxidation - Oxidationn Unclear [13]
MR004734 Metronidazole 5-amino Reduction - Reduction Unclear [13]
⏷ Show the Full List of 10 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[2]
Nitroreductase (NTR) DME1327 Enterococcus casseliflavus
A0A377KR04_ENTCA
1.5.1.39
[5]
Nitroreductase (NTR) DME1328 Enterococcus gallinarum
A0A376H6M5_ENTGA
1.5.1.39
[5]
Nitroreductase (NTR) DME1340 Bacteroides fragilis
A0A1C0X0J8_BACFG
1.5.1.39
[6] , [7]
Nitroreductase (NTR) DME1247 Enterobacter cloacae
NFSB_ENTCL
1.5.1.39
[8]
Nitroreductase (NTR) DME1064 Giardia intestinalis
A0A482G3K9_GIAIN
1.5.1.39
[9]
Nitroreductase (NTR) DME1065 Trichomonas vaginalis
A2DZ34_TRIVA
1.5.1.39
[9]
Nitroreductase (NTR) DME1245 Clostridium perfringens
B1R7B9_CLOPF
1.5.1.39
[10]
Nitroreductase (NTR) DME1066 Entamoeba histolytica
A4K8Z3_ENTHI
1.5.1.39
[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[11]
Unclear metabolic mechanism (DME-unclear) DME1260 Clostridium perfringens Not Available Not Available [10]
⏷ Show the Full List of 15  DME(s)
References
1 Metronidazole was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
3 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
4 Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? Ann Pharmacother. 2007 Apr;41(4):653-8.
5 Mechanism of metronidazole-resistance by isolates of nitroreductase-producing Enterococcus gallinarum and Enterococcus casseliflavus from the human intestinal tract. FEMS Microbiol Lett. 2003 Aug 29;225(2):195-200.
6 Isolation of metronidazole-resistant Bacteroides fragilis carrying the nimA nitroreductase gene from a patient in Washington State. J Clin Microbiol. 2004 Sep;42(9):4127-9. Case Reports
7 Biotransformation of 1-nitropyrene in intestinal anaerobic bacteria. Microbiol Immunol. 1982;26(11):993-1005.
8 Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
9 Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases). Antimicrob Agents Chemother. 2009 Feb;53(2):458-64.
10 Acetamide--a metabolite of metronidazole formed by the intestinal flora. Biochem Pharmacol. 1979 Dec 15;28(24):3611-5.
11 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
12 Disposition and metabolism of metronidazole in patients with liver failure
13 Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms
14 Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation

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