Details
Stereochemistry | RACEMIC |
Molecular Formula | C15H22N2O |
Molecular Weight | 246.348 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C2=CC=CC=C2
InChI
InChIKey=GJJFMKBJSRMPLA-HIFRSBDPSA-N
InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m1/s1
Molecular Formula | C15H22N2O |
Molecular Weight | 246.348 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/23499664Curator's Comment: https://www.tga.gov.au/sites/default/files/auspar-milnacipran-hydrochloride-120124.pdf
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664
Curator's Comment: https://www.tga.gov.au/sites/default/files/auspar-milnacipran-hydrochloride-120124.pdf
Dextromilnacipran (1R, 2S/F2696) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran is pharmacologically less active as compared with racemic mixture and levomilnacipran (1S, 2R/F2695).
Originator
Sources: http://adisinsight.springer.com/drugs/800000712 | https://www.google.com/patents/USRE43879
Curator's Comment: Milnacipran was synthesised as a racemic mixture at the PIERRE FABRE MEDICAMENT Research Centre (Castres, France).
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664 |
290.0 nM [Ki] | ||
Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664 |
16.9 nM [Ki] | ||
Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664 |
139.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | SAVELLA Approved UseSavella is indicated for the management of fibromyalgia. Savella is not approved for use in pediatric patients [see Use in Specific Populations (8.4) Launch Date2009 |
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Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
132 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26663198/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
150 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8923123/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1316.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26663198/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26663198/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8923123/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
6 h |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
87% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8923123/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
87% |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MILNACIPRAN 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 |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no | |||
Page: 18.0 |
no | |||
Page: 18.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no | |||
Page: 18.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no | |||
Page: 18.0 |
no | |||
Page: 18.0 |
no | |||
Page: 18.0 |
no | |||
Page: 18.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=27 Page: 27.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=7 Page: 7.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
no | no (co-administration study) Comment: no changes in PK of warfarin or milnacipran were observed Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
no | unlikely (co-administration study) Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
no | unlikely (co-administration study) Comment: At steady state, Cmax and AUC for milnacipran increased by only 10% and 20% when coadministered with levomepromazine; no changes in PK of warfarin or milnacipran were observed Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
no | unlikely (co-administration study) Comment: when coadministered with carbamazepine, exposure (Cmax and AUC) to milnacipran decreased by 18% and 19%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_ClinPharmR_P1.pdf#page=55 Page: 55.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022256s000_PharmR_P2.pdf#page=59 Page: 59.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Which bioequivalence study for a racemic drug? Application to milnacipran. | 1998 Apr-Jun |
|
[Pharmacokinetics and drug interactions of antidepressive agents]. | 2001 Aug |
|
[Serotonin-noradrenaline reuptake inhibitors(SNRIs)]. | 2001 Aug |
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Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. | 2001 May |
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Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? | 2002 |
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Elevation of blood pressure induced by high-dose milnacipran. | 2002 Dec |
|
Conformational analysis of the NMDA receptor antagonist (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) designed by a novel conformational restriction method based on the structural feature of cyclopropane ring. | 2002 Jul |
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Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in rats. | 2002 Jul |
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Blood concentration of milnacipran in a case of a fatal automobile accident. | 2002 Mar |
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Silent thyroiditis associated with short-term lithium therapy. | 2002 Nov-Dec |
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A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression. | 2002 Oct |
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Effect of chronic treatment with milnacipran on sleep architecture in rats compared with paroxetine and imipramine. | 2002 Oct |
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[Psychotropic drugs used in a psychiatric hospital (pharmaco-epidemiologic aspects)]. | 2003 |
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[Experience with ixel (milnacipran hydrochloride) use in the treatment of patients with post-stroke depression]. | 2003 |
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Differential period of onset of action of fluvoxamine, paroxetine and milnacipran for depression. | 2003 Aug |
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Milnacipran and pindolol: a randomized trial of reduction of antidepressant latency. | 2003 Dec |
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Differential effects of milnacipran, fluvoxamine and paroxetine for depression, especially in gender. | 2003 Dec |
|
A method for designing conformationally restricted analogues based on allylic strain: synthesis of a novel class of noncompetitive NMDA receptor antagonists having the acrylamide structure. | 2003 Dec 4 |
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Dual monoamine modulation for improved treatment of major depressive disorder. | 2003 Feb |
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New hope in the treatment of painful symptoms in depression. | 2003 Jan |
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Functional expression of the norepinephrine transporter in cultured rat astrocytes. | 2003 Jan |
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Milnacipran for the treatment of chronic pain. | 2003 Oct |
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Effect of pindolol and milnacipran versus milnacipran and placebo on plasma prolactin and adrenocorticotrophic hormone in depressed subjects. | 2003 Oct |
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Favorable effect of milnacipran on depression induced by interferon-alpha. | 2003 Spring |
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Efficacy of milnacipran for depressive symptoms in schizophrenia spectrum disorders. | 2004 Apr |
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Milnacipran treatment of a terminally ill cancer patient with major depressive disorder. | 2004 Aug |
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Ejaculation after defecation without orgasm induced by milnacipran. | 2004 Fall |
|
[Acute hepatitis associated with milnacipran treatment]. | 2004 Feb |
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Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol) levels and clinical responses with respect to milnacipran versus paroxetine treatment. | 2004 Feb |
|
Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. | 2004 Feb 1 |
|
Reboxetine: a norepinephrine selective reuptake pump inhibitor. | 2004 Jan |
|
Double-blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers. | 2004 Jan |
|
A case of temporo-mandibular disorder with fibromyalgia treated with the antidepressant, milnacipran. | 2004 Jul |
|
Augmentation of milnacipran by risperidone in treatment for major depression. | 2004 Mar |
|
Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors. | 2004 Mar 4 |
|
The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats. | 2004 May |
|
Differential effects of milnacipran, fluvoxamine and paroxetine for inhibited and agitated depression. | 2004 Nov |
|
A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. | 2004 Oct |
|
In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran. | 2004 Sep |
|
Effectiveness of milnacipran for the treatment of chronic pain: a case series. | 2004 Sep-Oct |
|
[Effects of milnacipran on neuronal excitability and synaptic transmission in neurons of the rat locus coeruleus]. | 2005 Jan |
|
Lithium augmentation in milnacipran-refractory depression for the prevention of relapse following electroconvulsive therapy. | 2005 Jan-Feb |
|
Anxiolytic-like effect of milnacipran in the four-plate test in mice: mechanism of action. | 2005 Jul |
|
The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain. | 2005 May |
|
Chronic treatment with milnacipran reverses the impairment of synaptic plasticity induced by conditioned fear stress. | 2005 May |
|
The effect of milnacipran (serotonin noradrenaline reuptake inhibitor) on memory in Korsakoff's syndrome after encephalitis. | 2005 May-Jun |
Sample Use Guides
The recommended dose of Savella (Milnacipran) is 100 mg/day (50 mg twice daily).
Based on efficacy and tolerability dosing may be titrated according to the following schedule:
Day 1: 12.5 mg once
Days 2-3: 25 mg/day (12.5 mg twice daily)
Days 4-7: 50 mg/day (25 mg twice daily)
After Day 7: 100 mg/day (50 mg twice daily)
Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily).
Doses above 200 mg/day have not been studied.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23499664
Milnacipran inhibits norepinephrine and serotonin reuptake in rat hypothalamic synaptosomes with IC50 values of 30 and 150 nM, respectively
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:32:43 GMT 2025
by
admin
on
Mon Mar 31 18:32:43 GMT 2025
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Record UNII |
G56VK1HF36
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29747
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WHO-VATC |
QN06AX17
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EMA ASSESSMENT REPORTS |
IMPULSOR (REFUSED, FIBROMYALGIA)
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NDF-RT |
N0000000109
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NCI_THESAURUS |
C265
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NDF-RT |
N0000175749
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NDF-RT |
N0000000102
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LIVERTOX |
NBK547960
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EMA ASSESSMENT REPORTS |
MILNACIPRAN PIERRE FABRE MEDICAMENT (REFUSED: FIBROMYALGIA)
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WHO-ATC |
N06AX17
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EMA ASSESSMENT REPORTS |
IMPULSOR (REFUSED: FIBROMYALGIA)
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C048107
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588250
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PRIMARY | RxNorm | ||
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MILNACIPRAN
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C78021
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7436
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CHEMBL259209
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G56VK1HF36
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100000080634
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DTXSID3048287
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m7545
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Milnacipran
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DB04896
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G56VK1HF36
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1808
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92623-85-3
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SUB08965MIG
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
URINE
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BINDER->LIGAND |
The plasma protein binding of milnacipran is approximately 13% and is independent of the concentration (Study# M013).
BINDING
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ENANTIOMER -> RACEMATE | |||
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ENANTIOMER -> RACEMATE |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
URINE
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE -> PARENT |
Lower than detection limit in plasma
MAJOR
URINE
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Absolute Bioavailability | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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