U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of FLUOXETINE

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

HIDE SMILES / InChI

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

Curator's Comment: # Eli Lilly

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PROZAC

Approved Use

Fluoxetine 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 Date

1987
Primary
PROZAC

Approved Use

Fluoxetine 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 Date

1987
Primary
PROZAC

Approved Use

Fluoxetine 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 Date

1987
Primary
PROZAC

Approved Use

Fluoxetine 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 Date

1987
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
22.56 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1101.46 ng × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
46.39 h
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
5.5%
FLUOXETINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical 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
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
Drug as victimTox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
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
Created
by admin
on Mon Mar 31 18:02:50 GMT 2025
Edited
by admin
on Mon Mar 31 18:02:50 GMT 2025
Record UNII
01K63SUP8D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NSC-283480
Preferred Name English
FLUOXETINE
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
fluoxetine [INN]
Common Name English
(±)-N-METHYL-3-PHENYL-3-((.ALPHA.,ALPHA.,.ALPHA.-TRIFLUORO-P-TOLYL)OXY)PROPYLAMINE
Common Name English
FLUOXETIN RATIOPHARM
Common Name English
DL-N-METHYL-3-(P-TRIFLUOROMETHYLPHENOXY)-3-PHENYLPROPYLAMINE
Common Name English
FLUOXETINE [USAN]
Common Name English
NSC-758685
Code English
Fluoxetine [WHO-DD]
Common Name English
FLUOXETINE [EMA EPAR VETERINARY]
Common Name English
FLUOXETINE [VANDF]
Common Name English
N-METHYL-.GAMMA.-(4-(TRIFLUOROMETHYL)PHENOXY)BENZENEPROPANAMINE
Systematic Name English
FLUOXETINE [MI]
Common Name English
FLUVAL
Common Name English
BENZENEPROPANAMINE, N-METHYL-G-(4-(TRIFLUOROMETHYL)PHENOXY)-, (±)-
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 183504
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
NDF-RT N0000000109
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-ATC N06AB03
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
EMA VETERINARY ASSESSMENT REPORTS RECONCILE [AUTHORIZED]
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
FDA ORPHAN DRUG 123199
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
LIVERTOX NBK548010
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-ATC N06CA03
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-VATC QN06AB03
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 24.2.1
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 8.4
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
NCI_THESAURUS C94725
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
CFR 21 CFR 520.980
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
NCI_THESAURUS C265
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
NDF-RT N0000175696
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
WHO-VATC QN06CA03
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
Code System Code Type Description
WIKIPEDIA
FLUOXETINE
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
MERCK INDEX
m5487
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY Merck Index
CAS
54910-89-3
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PRIMARY
ChEMBL
CHEMBL41
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PRIMARY
EVMPD
SUB07723MIG
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
FDA UNII
01K63SUP8D
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
DAILYMED
01K63SUP8D
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
DRUG CENTRAL
1209
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PRIMARY
NSC
283480
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PRIMARY
RXCUI
4493
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PRIMARY RxNorm
NCI_THESAURUS
C506
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PRIMARY
EPA CompTox
DTXSID7023067
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PRIMARY
IUPHAR
203
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PRIMARY
CHEBI
5118
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PRIMARY
PUBCHEM
3386
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PRIMARY
INN
3883
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PRIMARY
DRUG BANK
DB00472
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
MESH
D005473
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
NSC
758685
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
LACTMED
Fluoxetine
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
SMS_ID
100000092819
Created by admin on Mon Mar 31 18:02:50 GMT 2025 , Edited by admin on Mon Mar 31 18:02:50 GMT 2025
PRIMARY
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
MAXIMUM TOLERATED DOSE TOXICITY RAPID METABOLIZERS OR THOSE WITH INADEQUATE RESPONSE AFTER 8 WEEKS

Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC NORFLUOXETINE
PHARMACOKINETIC
NORFLUOXETINE, LIVER CIRRHOSIS
PHARMACOKINETIC
LIVER CIRRHOSIS
PHARMACOKINETIC