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

General Information of Drug (ID: DR0720)
Drug Name
Fluoxetine hydrochloride
Synonyms
Fluoxetina; Fluoxetina [INN-Spanish]; Fluoxetina [Spanish]; Fluoxetine [USAN:INN:BAN]; Fluoxetinum; Fluoxetinum [INN-Latin]; Fluval; Portal; Pulvules; fluoxetine; 54910-89-3; CHEMBL41; Eufor; Methyl-[3-phenyl-3-(4-trifluoromethyl-phenoxy)-propyl]-amine; N-Methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine; N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine; dl-3-(p-Trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine; Animex-On; Fluoxetin; Adofen; Affectine; Alzac 20; Deproxin; Digassim; Erocap; FLUOXETINE HYDROCHLORIDE; Fluctin; Fluctine; Fludac; Flufran; Flunil; Flunirin; Fluox-Puren; Fluoxac; Fluoxeren; Fluoxetine (hydrochloride); Fluoxetine Hcl; Fluoxetine.HCl; Fluoxil; Flutin; Flutine; Fluxen; Fluxil; Foxetin; LY-110140; Lilly 110140; Lorien; Margrilan; Modipran; Neupax; Nopres; Oxedep; Pragmaten; Prizma; Proctin; Prodep; Prozac; Prozac 20; Rowexetina; Sanzur; Sarafem; Selfemra; Sinzac; Zactin; 56296-78-7; 59333-67-4; CCRIS 6150; Lovan; Nuzak; Zepax
Indication Depression [ICD11: 6A71] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 345.8 Topological Polar Surface Area 21.3
Heavy Atom Count 23 Rotatable Bond Count 6
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
62857
ChEBI ID
CHEBI:145458
CAS Number
56296-78-7
TTD Drug ID
D0TR5X
Formula
C17H19ClF3NO
Canonical SMILES
CNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F.Cl
InChI
1S/C17H18F3NO.ClH/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20;/h2-10,16,21H,11-12H2,1H3;1H
InChIKey
GIYXAJPCNFJEHY-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
4-Trifluoromethylphenol DM004668
67874
Oxidation - O-dealkylation 1 [7] , [11]
Fluoxetine glucuronide DM004672
154699931
Conjugation - Glucuronidation 1 [12]
Norfluoxetine DM004667
4541
Oxidation - N-demethylation 1 [9] , [12] , [5] , [11]
4-Trifluoromethylphenol DM004668
67874
Oxidation - O-dealkylation 2 [13]
Midostaurin Metabolite P6B DM001361
464
Oxidation - O-dealkylation 2 [13]
Norfluoxetine alcohol DM004669
72756505
Oxidation - Oxidationn deamination 2 [12]
Norfluoxetine glucuronide DM004671
131770058
Conjugation - Glucuronidation 2 [9]
Midostaurin Metabolite P6B DM001361
464
Oxidation - O-dealkylation 3 [13]
Norfluoxetine acid DM004670
85432033
Oxidation - Oxidationn 3 [12]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005012 Fluoxetine hydrochloride Norfluoxetine Oxidation - N-demethylation CYP2D6 ... [9], [12], [5], [11]
MR005018 Fluoxetine hydrochloride 4-Trifluoromethylphenol Oxidation - O-dealkylation CYP2C19 ... [7], [11]
MR005019 Fluoxetine hydrochloride Fluoxetine glucuronide Conjugation - Glucuronidation UGT2A1 [12]
MR005013 Norfluoxetine 4-Trifluoromethylphenol Oxidation - O-dealkylation CYP2C19 ... [13]
MR005015 Norfluoxetine Norfluoxetine alcohol Oxidation - Oxidationn deamination Unclear [12]
MR005017 Norfluoxetine Norfluoxetine glucuronide Conjugation - Glucuronidation UGT2A1 [9]
MR005014 4-Trifluoromethylphenol Hippuric acid Oxidation - O-dealkylation CYP2C19 ... [13]
MR005016 Norfluoxetine alcohol Norfluoxetine acid Oxidation - Oxidationn Unclear [12]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[7]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[8]
UDP-glucuronosyltransferase 2A1 (UGT2A1) DME0622 Homo sapiens
UD2A1_HUMAN
2.4.1.17
[9]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1257 Bifidobacterium longum Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1265 Escherichia coli Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1267 Anaerobutyricum hallii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1357 Alistipes indistinctus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1366 Bacteroides eggerthii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1375 Bacteroides intestinalis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1376 Bacteroides ovatus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1377 Bacteroides pectinophilus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1378 Bacteroides uniformis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1379 Bacteroides stercoris Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1386 Bifidobacterium adolescentis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1388 Bifidobacterium breve Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1391 Bifidobacterium ruminatum Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1398 Clostridioides difficile Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1399 Enterocloster asparagiformis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1400 Enterocloster bolteae Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1404 Clostridium sporogenes Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1412 Dorea formicigenerans Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1416 Enterobacter cancerogenus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1418 Enterococcus faecalis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1420 Erysipelatoclostridium ramosum Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1425 Eubacterium rectale Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1427 Eubacterium ventriosum Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1431 Holdemanella biformis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1435 Lactobacillus reuteri Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1446 Parabacteroides johnsonii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1447 Parabacteroides merdae Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1449 Prevotella copri Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1451 Proteus penneri Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1454 Providencia stuartii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1456 Roseburia intestinalis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1458 Ruminococcus gnavus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1459 Ruminococcus lactaris Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1462 Salmonella enterica Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1467 Subdoligranulum variabile Not Available Not Available [10]
⏷ Show the Full List of 54  DME(s)
References
1 Fluoxetine Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Clinically significant psychotropic drug-drug interactions in the primary care setting. Curr Psychiatry Rep. 2012 Aug;14(4):376-90.
3 Molecular characterization of CYP2B6 substrates. Curr Drug Metab. 2008 Jun;9(5):363-73.
4 Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism. Med Chem. 2009 May;5(3):263-70.
5 (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos. 2000 Oct;28(10):1187-91.
6 Antidepressant drugs in the elderly--role of the cytochrome P450 2D6. World J Biol Psychiatry. 2003 Apr;4(2):74-80.
7 O-Dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes. J Pharmacol Exp Ther. 2002 Jan;300(1):105-11.
8 Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes. Acta Pharmacol Sin. 2001 Jan;22(1):85-90.
9 Pharmacogenomics knowledge for personalized medicine Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.
10 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
11 Simultaneous identification and quantitation of fluoxetine and its metabolite, norfluoxetine, in biological samples by GC-MS
12 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
13 DrugBank(Pharmacology-Metabolism):Fluoxetine hydrochloride

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