Details
Stereochemistry | ACHIRAL |
Molecular Formula | C9H8ClN5S |
Molecular Weight | 253.711 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
ClC1=C(NC2=NCCN2)C3=NSN=C3C=C1
InChI
InChIKey=XFYDIVBRZNQMJC-UHFFFAOYSA-N
InChI=1S/C9H8ClN5S/c10-5-1-2-6-8(15-16-14-6)7(5)13-9-11-3-4-12-9/h1-2H,3-4H2,(H2,11,12,13)
Molecular Formula | C9H8ClN5S |
Molecular Weight | 253.711 |
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/DB00697 | https://www.drugs.com/tizanidine.html | http://reference.medscape.com/drug/zanaflex-tizanidine-343071
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB00697 | https://www.drugs.com/tizanidine.html | http://reference.medscape.com/drug/zanaflex-tizanidine-343071
Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons. Side effects include dizziness, drowsiness, weakness, nervousness, hallucinations, depression, vomiting, dry mouth, constipation, diarrhea, stomach pain, heartburn, increased muscle spasms, back pain, rash, sweating, and a tingling sensation in the arms, legs, hands, and feet.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095158 |
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Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15481719 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZANAFLEX Approved UseTizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1) Launch Date8.4905283E11 |
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Primary | ZANAFLEX Approved UseTizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1) Launch Date8.4905283E11 |
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Primary | ZANAFLEX Approved UseTizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1) Launch Date8.4905283E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
11 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
54 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIZANIDINE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Disc. AE: Drowsiness, Fatigue... AEs leading to discontinuation/dose reduction: Drowsiness (5.9%) Sources: Page: p.716Fatigue (3.9%) Muscular weakness (3.9%) Affective disorder (3.9%) Bradycardia (2%) Ventricular extrasystoles (2%) Anxiety (2%) Sleep disturbance (2%) Syncope (2%) |
12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
Disc. AE: Hypotension, Liver injury... AEs leading to discontinuation/dose reduction: Hypotension Sources: Page: p.1Liver injury Sedation Hallucinations Renal impairment |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Anxiety | 2% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Bradycardia | 2% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Sleep disturbance | 2% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Syncope | 2% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Ventricular extrasystoles | 2% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Affective disorder | 3.9% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Fatigue | 3.9% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Muscular weakness | 3.9% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Drowsiness | 5.9% Disc. AE |
19.36 mg 3 times / day multiple, oral (mean) Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: Page: p.716 |
unhealthy, 18 - 77 n = 51 Health Status: unhealthy Condition: Spasticity Age Group: 18 - 77 Sex: M+F Population Size: 51 Sources: Page: p.716 |
Hallucinations | Disc. AE | 12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
Hypotension | Disc. AE | 12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
Liver injury | Disc. AE | 12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
Renal impairment | Disc. AE | 12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
Sedation | Disc. AE | 12 mg 3 times / day multiple, oral Recommended Dose: 12 mg, 3 times / day Route: oral Route: multiple Dose: 12 mg, 3 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Spasticity Sources: Page: p.1 |
PubMed
Title | Date | PubMed |
---|---|---|
Development of a simple spasticity quantification method: effects of tizanidine on spasticity in patients with sequelae of cerebrovascular disease. | 1992 Feb |
|
Anti-spasticity agents for multiple sclerosis. | 2001 |
|
Chronic blockade of melanocortin receptors alleviates allodynia in rats with neuropathic pain. | 2001 Dec |
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Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery. | 2001 Jan |
|
Treatment of spasticity. | 2002 Jun |
|
Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache. | 2002 Mar |
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[Spastic syndrome and main directions of its treatment]. | 2003 |
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Anti-spasticity agents for multiple sclerosis. | 2003 |
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Preventative treatment for migraine and tension-type headaches : do drugs having effects on muscle spasm and tone have a role? | 2003 |
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[Intrathecal baclofen in the treatment of severe spastic tetraplegia and dystonia in children and adolescents]. | 2003 Apr 21 |
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Effects of intrathecally administered dexmedetomidine, MPV-2426 and tizanidine on EMG in rats. | 2003 Mar |
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Continuous intrathecal clonidine and tizanidine in conscious dogs: analgesic and hemodynamic effects. | 2003 Mar |
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Stability-indicating HPTLC determination of tizanidine hydrochloride in bulk drug and pharmaceutical formulations. | 2003 Nov 24 |
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A benefit-risk assessment of baclofen in severe spinal spasticity. | 2004 |
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Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. | 2004 Aug |
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Modulation of the transmission in group II heteronymous pathways by tizanidine in spastic hemiplegic patients. | 2004 Jan |
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Tizanidine for the treatment of intention myoclonus: a case series. | 2004 Jul |
|
Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection. | 2004 Jul 5 |
|
Prophylactic migraine therapy: emerging treatment options. | 2004 Jun |
|
Hypotension due to interaction between lisinopril and tizanidine. | 2004 Nov |
|
[Progressive encephalomyelitis with rigidity responsive to gabapentin: a pharmacological update]. | 2004 Oct |
|
Involuntary jerking of lower half of the body (spinal myoclonus). | 2005 Feb |
|
Application of HPLC and HPTLC for the simultaneous determination of tizanidine and rofecoxib in pharmaceutical dosage form. | 2005 Feb 7 |
|
Assessment of efficacy and psychomotor performances of thiocolchicoside and tizanidine in patients with acute low back pain. | 2005 Jul |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes. | 2005 Sep |
|
Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. | 2005 Sep-Oct |
|
Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension-type headache: evaluation of efficacy and impact on quality of life. | 2006 Feb |
|
[The study and treatment of dystonias in childhood]. | 2006 Oct 10 |
Patents
Sample Use Guides
Recommended starting dose: 2 mg; dose can be repeated at 6 to 8 hour
intervals, up to a maximum of 3 doses in 24 hours
Dosage can be increased by 2 mg to 4 mg per dose, with 1 to 4 days
between increases; total daily dose should not exceed 36 mg
Tizanidine pharmacokinetics differs between tablets and capsules, and
when taken with or without food. These differences could result in a
change in tolerability and control of symptoms
To discontinue Zanaflex, decrease dose slowly to minimize the risk of
withdrawal and rebound hypertension, tachycardia, and hypertonia
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1331591
Male Wi star rats (300-350g) were decapitated and the kidneys were rapidly removed. The kidneys were minced in ice-cold 50 mM Tris-HCI, 5 mM EDTA (pH 7.7) and then homogenized by a polytron. The homogenate was filtered through 4 layers of silk gauze. and centrifuged at 40,000 X g for 13 min. The pellet was resuspended in 50 mM Tris-HCI, 25 mM NaCI buffer (pH 7.7), incubated for 30 min at 25°C, and recen trifuged as described above. The final pellet was resuspended in 50 mM Tris-HC1 buffer (pH 7.7) and used for the binding assay. Incubations were performed in duplicate at 25°C for
40 min in a total volume of 1 ml. The incubate consisted of 3H p-aminoclonidine (3H-PAC), a suspension of kidney membranes (approximately 0.55 mg/ml) and either buffer alone or buffer containing Tizanidine. Non-specific binding was defined by parallel incubations containing 10,uM phentolamine. In experiments using adrenaline, all samples contained ascortic acid in a final concentration of 0.01%. Incubations were terminated by vacuum filtration over Whatman GF/C filters by using a cell harvester. The filters were washed with ice-cold Tris-HCI; then the filter-bound radioactivity was determined using a scintillation counter (Aloka, Japan).
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:17:18 UTC 2023
by
admin
on
Fri Dec 15 15:17:18 UTC 2023
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Record UNII |
6AI06C00GW
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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WHO-ATC |
M03BX02
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WHO-VATC |
QM03BX02
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NCI_THESAURUS |
C29709
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LIVERTOX |
NBK548048
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NDF-RT |
N0000175554
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NDF-RT |
N0000009918
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100000082123
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2683
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C023754
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CHEMBL1079
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63629
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5487
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6AI06C00GW
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57258
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m10912
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7308
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51322-75-9
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SUB11129MIG
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TIZANIDINE
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6AI06C00GW
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DTXSID9023679
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4697
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C61976
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DB00697
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> SUBSTRATE |
IN MICROSOMES
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SALT/SOLVATE -> PARENT | |||
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TARGET -> AGONIST |
SHORT-ACTING
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EXCRETED UNCHANGED |
URINE
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE INACTIVE -> PARENT |
MAJOR
PLASMA; URINE
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
MINOR
URINE
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METABOLITE INACTIVE -> PARENT |
MAJOR
PLASMA; URINE
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METABOLITE -> PARENT |
MINOR
PLASMA; URINE
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METABOLITE -> PARENT |
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ACTIVE MOIETY |