Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C17H18F3NO |
| Molecular Weight | 309.3261 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCCC(OC1=CC=C(C=C1)C(F)(F)F)C2=CC=CC=C2
InChI
InChIKey=RTHCYVBBDHJXIQ-UHFFFAOYSA-N
InChI=1S/C17H18F3NO/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
| Molecular Formula | C17H18F3NO |
| Molecular Weight | 309.3261 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). Fluoxetine is a racemic mixture of the R- and S- enantiomers and are of equivalent pharmacologic activity. Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Fluoxetine is marketed under the trade names Prozac and Sarafem among others. It is also marketed for
the treatment of premenstrual dysphoric disorder (Sarafem®, fluoxetine hydrochloride). PROZAC is a selective serotonin reuptake inhibitor indicated for:
• Acute and maintenance treatment of Major Depressive Disorder (MDD)
in adult and pediatric patients aged 8 to 18 years
• Acute and maintenance treatment of Obsessive Compulsive
Disorder (OCD) in adult and pediatric patients aged 7 to 17 years
• Acute and maintenance treatment of Bulimia Nervosa in adult patients
• Acute treatment of Panic Disorder, with or without agoraphobia, in adult
patients.
Studies at clinically relevant doses in man have demonstrated that fluoxetine blocks the uptake of serotonin into human
platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine.
Antagonism of muscarinic, histaminergic, and α1-adrenergic receptors has been hypothesized to be associated with various
anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressant (TCA) drugs. Fluoxetine binds to these and
other membrane receptors from brain tissue much less potently in vitro than do the tricyclic drugs.
Originator
Sources: http://adisinsight.springer.com/drugs/800013380
Curator's Comment: # Eli Lilly
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 10.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | PROZAC Approved UseFluoxetine is a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) Fluoxetine and olanzapine in combination for: Acute treatment of Depressive Episodes Associated with Bipolar I Disorder in adults (1.5) 1.1 Major Depressive Disorder Fluoxetine hydrochloride is indicated for the acute and maintenance treatment of Major Depressive Disorder in adult patients and in pediatric patients aged 8 to18 years [see CLINICAL STUDIES (14.1) Launch Date1987 |
|||
| Primary | PROZAC Approved UseFluoxetine is a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) Fluoxetine and olanzapine in combination for: Acute treatment of Depressive Episodes Associated with Bipolar I Disorder in adults (1.5) 1.1 Major Depressive Disorder Fluoxetine hydrochloride is indicated for the acute and maintenance treatment of Major Depressive Disorder in adult patients and in pediatric patients aged 8 to18 years [see CLINICAL STUDIES (14.1) Launch Date1987 |
|||
| Primary | PROZAC Approved UseFluoxetine is a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) Fluoxetine and olanzapine in combination for: Acute treatment of Depressive Episodes Associated with Bipolar I Disorder in adults (1.5) 1.1 Major Depressive Disorder Fluoxetine hydrochloride is indicated for the acute and maintenance treatment of Major Depressive Disorder in adult patients and in pediatric patients aged 8 to18 years [see CLINICAL STUDIES (14.1) Launch Date1987 |
|||
| Primary | PROZAC Approved UseFluoxetine is a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) Fluoxetine and olanzapine in combination for: Acute treatment of Depressive Episodes Associated with Bipolar I Disorder in adults (1.5) 1.1 Major Depressive Disorder Fluoxetine hydrochloride is indicated for the acute and maintenance treatment of Major Depressive Disorder in adult patients and in pediatric patients aged 8 to18 years [see CLINICAL STUDIES (14.1) Launch Date1987 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
22.56 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15968712 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
13576.38 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16229112 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1101.46 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15968712 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
788626.72 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16229112 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
46.39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15968712 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
49.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16229112 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
FLUOXETINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.5% |
FLUOXETINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| moderate [IC50 31 uM] | ||||
| moderate | ||||
| moderate | ||||
| moderate | yes (co-administration study) Comment: addition of fluoxetine 20 mg/day to pre-existing risperidone therapy produced a mean 4- fold increase in plasma risperidone concentration, with some patients exhibiting an increase as large as 10-fold Sources: https://pubmed.ncbi.nlm.nih.gov/12172343/ |
|||
Sources: https://pubmed.ncbi.nlm.nih.gov/31037729/ |
no | |||
| strong [IC50 1.05 uM] | yes (co-administration study) Comment: Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution |
|||
| yes [IC50 14 uM] | ||||
| yes [IC50 16 uM] | ||||
| yes [IC50 3.32 uM] | ||||
| yes [IC50 30 uM] | ||||
| yes [IC50 5 uM] | ||||
| yes [IC50 6.2 uM] | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: Fluoxetine dosing inhibited CYP2C19 activity in both age groups, increasing the (S)- to (R)-mephenytoin ratio 3- to 4-fold Sources: https://pubmed.ncbi.nlm.nih.gov/11270912/ |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| minor | ||||
| yes [Ki 19 uM] | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effects of selective serotonin reuptake inhibitors on sexual function. | 2001-04 |
|
| Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. | 2001-04 |
|
| Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin. | 2001-04 |
|
| Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers. | 2001-04 |
|
| Serotonergic manipulations both potentiate and reduce brain stimulation reward in rats: involvement of serotonin-1A receptors. | 2001-04 |
|
| Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors. | 2001-04 |
|
| Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test. | 2001-04 |
|
| Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys. | 2001-04 |
|
| Modafinil does not affect serotonin efflux from rat frontal cortex synaptosomes: comparison with known serotonergic drugs. | 2001-03-16 |
|
| Repeated electroconvulsive stimulation, but not antidepressant drugs, induces mossy fibre sprouting in the rat hippocampus. | 2001-03-02 |
|
| Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus. | 2001-03-01 |
|
| Mutism: elective or selective, and acquired. | 2001-03 |
|
| Regulation of the vesicular monoamine transporter-2: a novel mechanism for cocaine and other psychostimulants. | 2001-03 |
|
| Role of serotonin and noradrenaline in social dysfunction: a review of data on reboxetine and the Social Adaptation Self-evaluation Scale (SASS). | 2001-02-28 |
|
| Fluoxetine (Prozac) as a cause of QT prolongation. | 2001-02-26 |
|
| Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity. | 2001-02-23 |
|
| A compulsive collecting behavior following an A-com aneurysmal rupture. | 2001-02-13 |
|
| Fluoxetine and side effects in the geriatric population. | 2001-02-01 |
|
| Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats. | 2001-02 |
|
| Characterization of 5-HT receptors in the parasitic nematode, Ascaris suum. | 2001-02 |
|
| Subjective and discriminative stimulus effects of two de-nicotinized cigarettes with different tar yields. | 2001-02 |
|
| [Effect of fluoxetine on histamine content in the rat conjunctiva]. | 2001-02 |
|
| Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment. | 2001-02 |
|
| Severe symptomatic hyponatremia during citalopram therapy. | 2001-02 |
|
| Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers. | 2001-02 |
|
| Reversible galactorrhea and prolactin elevation related to fluoxetine use. | 2001-02 |
|
| Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers. | 2001-02 |
|
| Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo. | 2001-02 |
|
| Augmentation of fluoxetine's antidepressant action by pindolol: analysis of clinical, pharmacokinetic, and methodologic factors. | 2001-02 |
|
| The economic consequences of a drug-drug interaction. | 2001-02 |
|
| Dose-dependent seizure activity associated with fluoxetine therapy. | 2001-02 |
|
| Acute hypokalemic paralysis associated with long-term lithium therapy. | 2001-02 |
|
| Psychopharmacologic treatment of adolescent depression. | 2001-02 |
|
| Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice. | 2001-01-31 |
|
| Fluoxetine (Sarafem) for premenstrual dysphoric disorder. | 2001-01-22 |
|
| Fluoxetine in the treatment of Huntington's disease. | 2001-01-01 |
|
| [Ten questions on the treatment of obesity: from dieting to surgery]. | 2001-01 |
|
| Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients. | 2001-01 |
|
| Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. | 2001-01 |
|
| Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. | 2001-01 |
|
| Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania. | 2001-01 |
|
| Fluoxetine-induced Ca2+ signals in Madin-Darby canine kidney cells. | 2001-01 |
|
| Central 5-hydroxytryptamine-2A receptor expression in transgenic mice bearing a glucocorticoid receptor antisense. | 2001-01 |
|
| Adding group psychotherapy to medication treatment in dysthymia: a randomized prospective pilot study. | 2001 |
|
| Evidence of early onset of antidepressant effect in randomized controlled trials. | 2001 |
|
| The effects of antidepressants on sexual functioning in depressed patients: a review. | 2001 |
|
| Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. | 2001 |
|
| Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants. | 2001 |
|
| Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness. | 2001 |
|
| Urinary retention with reboxetine-fluoxetine combination in a young man. | 2000-12 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/fluoxetine.html
Usual Adult Dose for Bulimia
Immediate-release oral formulations:
Recommended dose: 60 mg orally once a day
Usual Adult Dose for Depression
Immediate-release oral formulations:
Initial dose: 20 mg orally once a day, increased after several weeks if insufficient clinical improvement is observed
Maintenance dose: 20 to 60 mg orally per day
Maximum dose: 80 mg orally per day
Delayed release oral capsules:
Initial dose: 90 mg orally once a week, commenced 7 days after the last daily dose of immediate-release fluoxetine 20 mg formulations.
Usual Adult Dose for Obsessive Compulsive Disorder
Immediate-release oral formulations:
Initial dose: 20 mg orally once a day, increased after several weeks if insufficient clinical improvement is observed.
Maintenance dose: 20 to 60 mg orally per day
Maximum dose: 80 mg orally per day
Usual Adult Dose for Panic Disorder
Immediate-release oral formulations:
Initial dose: 10 mg orally once a day, increased after one week to 20 mg orally once a day
Maintenance dose: 20 to 60 mg orally per day
Maximum dose: 60 mg orally per day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16601320
Caco-2 SERT was also shown to be a high affinity (Kt=0.216 uM) saturable, Na(+) -dependent transporter that was inhibited by fluoxetine (IC(50)=17.6 nM).
| Substance Class |
Chemical
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| Record UNII |
01K63SUP8D
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Validated (UNII)
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| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
183504
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NDF-RT |
N0000000109
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WHO-ATC |
N06AB03
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EMA VETERINARY ASSESSMENT REPORTS |
RECONCILE [AUTHORIZED]
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FDA ORPHAN DRUG |
123199
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LIVERTOX |
NBK548010
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WHO-ATC |
N06CA03
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WHO-VATC |
QN06AB03
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WHO-ESSENTIAL MEDICINES LIST |
24.2.1
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WHO-ESSENTIAL MEDICINES LIST |
8.4
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NCI_THESAURUS |
C94725
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CFR |
21 CFR 520.980
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NCI_THESAURUS |
C265
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NDF-RT |
N0000175696
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WHO-VATC |
QN06CA03
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| Code System | Code | Type | Description | ||
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FLUOXETINE
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m5487
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54910-89-3
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CHEMBL41
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SUB07723MIG
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01K63SUP8D
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01K63SUP8D
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1209
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283480
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4493
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C506
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DTXSID7023067
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203
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5118
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3386
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3883
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DB00472
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D005473
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758685
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Fluoxetine
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100000092819
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> INHIBITOR |
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METABOLIC ENZYME -> INHIBITOR |
Moderate inhibitor
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TARGET -> INHIBITOR |
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METABOLIC ENZYME -> INHIBITOR |
Strong inhibitor
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SALT/SOLVATE -> PARENT |
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLITE -> PARENT |
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| MAXIMUM TOLERATED DOSE | TOXICITY |
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RAPID METABOLIZERS OR THOSE WITH INADEQUATE RESPONSE AFTER 8 WEEKS |
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| Tmax | PHARMACOKINETIC |
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| Biological Half-life | PHARMACOKINETIC |
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NORFLUOXETINE PHARMACOKINETIC PHARMACOKINETIC PHARMACOKINETIC |
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