Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H22ClN5O |
Molecular Weight | 371.8645 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
c1ccn2c(c1)nn(CCCN3CCN(CC3)c4cccc(c4)Cl)c2=O
InChI
InChIKey=PHLBKPHSAVXXEF-UHFFFAOYSA-N
InChI=1S/C19H22ClN5O/c20-16-5-3-6-17(15-16)23-13-11-22(12-14-23)8-4-10-25-19(26)24-9-2-1-7-18(24)21-25/h1-3,5-7,9,15H,4,8,10-14H2
Molecular Formula | C19H22ClN5O |
Molecular Weight | 371.8645 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment:: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB00656 | https://www.drugs.com/trazodone.html | http://reference.medscape.com/drug/oleptro-trazodone-d-342965
Curator's Comment:: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB00656 | https://www.drugs.com/trazodone.html | http://reference.medscape.com/drug/oleptro-trazodone-d-342965
Trazodone (brand name Oleptro, Desyrel, etc) is a serotonin uptake inhibitor that is used as an antidepressive agent. Trazodone binds to the 5-HT2 receptor, it acts as a serotonin agonist at high doses and a serotonin antagonist at low doses. Like fluoxetine, trazodone's antidepressant activity likely results from blockage of serotonin reuptake by inhibiting serotonin reuptake pump at the presynaptic neuronal membrane. If used for long time periods, postsynaptic neuronal receptor binding sites may also be affected. The sedative effect of trazodone is likely the result of alpha-adrenergic blocking action and modest histamine blockade at the H1 receptor. It weakly blocks presynaptic alpha2-adrenergic receptors and strongly inhibits postsynaptic alpha1 receptors. Trazodone does not affect the reuptake of norepinephrine or dopamine within the CNS. Because of its lack of anticholinergic side effects, trazodone is especially useful in situations in which antimuscarinic effects are particularly problematic (e.g., in patients with benign prostatic hyperplasia, closed-angle glaucoma, or severe constipation). Trazodone's propensity to cause sedation is a dual-edged sword. For many patients, the relief from agitation, anxiety, and insomnia can be rapid; for other patients, including those individuals with considerable psychomotor retardation and feelings of low energy, therapeutic doses of trazodone may not be tolerable because of sedation. Trazodone elicits orthostatic hypotension in some patients, probably as a consequence of α1-adrenergic receptor blockade. Mania has been observed in association with trazodone treatment, including in patients with bipolar disorder, as well as in patients with previous diagnoses of major depression. Compared to the reversible MAOI antidepressant drug moclobemide, significantly more impairment of vigilance occurs with trazodone.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703 |
17.0 nM [IC50] | ||
Target ID: CHEMBL2096904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703 |
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Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568799 |
223.87 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date3.78000015E11 |
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Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date3.78000015E11 |
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Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date3.78000015E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.88 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5% |
unknown, oral |
TRAZODONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Disc. AE: Drowsiness, Hypertension... AEs leading to discontinuation/dose reduction: Drowsiness (1 patient) Sources: Hypertension (1 patient) Vomiting (1 patient) |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Disc. AE: Dry mouth, Upset stomach... AEs leading to discontinuation/dose reduction: Dry mouth (1 patient) Sources: Upset stomach (1 patient) Drowsiness (1 patient) |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Disc. AE: Seizures, Hyponatremia... AEs leading to discontinuation/dose reduction: Seizures (grade 5, 1 patient) Sources: Hyponatremia (grade 5, 1 patient) |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: |
unknown, 55 years n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 Sources: |
Disc. AE: Arrhythmia... AEs leading to discontinuation/dose reduction: Arrhythmia (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Drowsiness | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Hypertension | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Vomiting | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Drowsiness | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Dry mouth | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Upset stomach | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Hyponatremia | grade 5, 1 patient Disc. AE |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Seizures | grade 5, 1 patient Disc. AE |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Arrhythmia | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: |
unknown, 55 years n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 23 uM] | ||||
yes [IC50 43 uM] | ||||
yes [IC50 45 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/11452702/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | yes (co-administration study) Comment: [PMID:7482685]: CYP2D6-mediated metabolism of trazodone is inhibited by coadministration of thioridazine, which is an inhibitor of this isozyme. |
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yes | yes (co-administration study) Comment: [DESYREL® LABEL]: The concomitant use of DESYREL and strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of DESYREL alone. The concomitant use of DESYREL and strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of DESYREL alone. |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Fluoxetine-induced sexual dysfunction reversed by trazodone. | 2000 Nov |
|
Interactions between herbal medicines and prescribed drugs: a systematic review. | 2001 |
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The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism. | 2001 Apr |
|
Acute trazodone and quipazine treatment attenuates apomorphine-induced aggressive behaviour in male rats without major impact on emotional behaviour or monoamine content post mortem. | 2001 Apr |
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Venlafaxine- and trazodone-induced serotonin syndrome. | 2001 Dec |
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Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers. | 2001 Dec |
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Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia. | 2001 Feb |
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Treatment of the agitation of late-life psychosis and Alzheimer's disease. | 2001 Jan |
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Antidepressants as analgesics: a review of randomized controlled trials. | 2001 Jan |
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Weight outcomes among antidepressant users in nursing facilities. | 2001 Jan |
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Fatal overdose with trazodone: case report and literature review. | 2001 Jul-Aug |
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Possible mild serotonin syndrome related to co-prescription of tandospirone and trazodone. | 2001 Mar-Apr |
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Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients. | 2001 May |
|
Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man. | 2001 Nov |
|
The treatment of generalised anxiety disorder. A systematic review. | 2002 Dec |
|
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. | 2002 Feb |
|
alpha(1)-Adrenoceptor antagonists. Rational design, synthesis and biological evaluation of new trazodone-like compounds. | 2002 Feb 11 |
|
Pharmacological aspects of erectile dysfunction. | 2002 Jun |
|
No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients. | 2002 Summer |
|
Mianserin and trazodone significantly attenuate the intensity of opioid withdrawal symptoms in mice. | 2003 Mar |
|
Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway. | 2003 Mar |
|
A fatal drug interaction between oxycodone and clonazepam. | 2003 May |
Sample Use Guides
Starting dose: 150 mg once daily. May be increased by 75 mg per day
every three days. Maximum dose: 375 mg per day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703
The receptors affinity was estimated at Nova Screen Laboratories by the ability of the Trazodone to displace selective radioligands. The assays were carried out using the following: for 5HT2A – rat cortical membranes, [3H]ketanserin (1.0 nM) as radioligand and methysergide as reference compound; for alpha1 - rat cortical membranes, [3H]prazosin (0.5 nM) and prazosin; for 5HT-R - rat forebrain membranes, [3H]citalopram (0.7 nM) and imipramine. In the preliminary binding assay, the results are expressed as inhibition percentage compared to results without drug and represent the average of duplicate tubes at each tested concentration in a single experiment.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Jun 26 05:54:09 UTC 2021
by
admin
on
Sat Jun 26 05:54:09 UTC 2021
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Record UNII |
YBK48BXK30
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Record Status |
Validated (UNII)
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Record Version |
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-
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Official Name | English | ||
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Brand Name | English | ||
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Systematic Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Systematic Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Code | English |
Classification Tree | Code System | Code | ||
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WHO-ATC |
N06AX05
Created by
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WHO-VATC |
QN06AX05
Created by
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LIVERTOX |
991
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NDF-RT |
N0000175696
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NCI_THESAURUS |
C265
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FDA ORPHAN DRUG |
593917
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Code System | Code | Type | Description | ||
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213
Created by
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PRIMARY | |||
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TRAZODONE
Created by
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PRIMARY | |||
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19794-93-5
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PRIMARY | |||
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D014196
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PRIMARY | |||
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2717
Created by
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PRIMARY | |||
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DB00656
Created by
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PRIMARY | |||
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7048
Created by
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PRIMARY | |||
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CHEMBL621
Created by
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PRIMARY | |||
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SUB11224MIG
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PRIMARY | |||
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10737
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PRIMARY | RxNorm | ||
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19794-93-5
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PRIMARY | |||
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M11010
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PRIMARY | Merck Index | ||
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5533
Created by
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PRIMARY | |||
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2878
Created by
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PRIMARY | |||
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C29510
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PRIMARY | |||
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YBK48BXK30
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PRIMARY | |||
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Trazodone
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PRIMARY | |||
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243-317-1
Created by
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PRIMARY |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLITE ACTIVE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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EFFECT OF FOOD PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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ORAL BIOAVAILABILITY | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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EXTENDED RELEASE PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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PROTEIN BINDING | PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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Route of Elimination | PHARMACOKINETIC |
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EXCRETED UNCHANGED PHARMACOKINETIC |
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Route of Elimination | PHARMACOKINETIC |
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Route of Elimination | PHARMACOKINETIC |
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