Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C10H8F2N4O |
| Molecular Weight | 238.1935 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=CN(CC2=C(F)C=CC=C2F)N=N1
InChI
InChIKey=POGQSBRIGCQNEG-UHFFFAOYSA-N
InChI=1S/C10H8F2N4O/c11-7-2-1-3-8(12)6(7)4-16-5-9(10(13)17)14-15-16/h1-3,5H,4H2,(H2,13,17)
| Molecular Formula | C10H8F2N4O |
| Molecular Weight | 238.1935 |
| 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:
http://www.rxlist.com/banzel-drug.htm
https://www.drugs.com/mtm/rufinamide.html
Curator's Comment: description was created based on several sources, including:
http://www.rxlist.com/banzel-drug.htm
https://www.drugs.com/mtm/rufinamide.html
Rufinamide is an anti-epileptic drug that is FDA approved for the treatment of lennox-gastaut syndrome (LGS). The principal mechanism of action of rufinamide is modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the channel. Hormonal contraceptives may be less effective with rufinamide. Patients on valproate should begin at a rufinamide dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults). Common adverse reactions include headache, dizziness, fatigue, somnolence, and nausea.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL4296 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23221868 |
3.8 µM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Palliative | BANZEL Approved UseI NDICATIONS AND USAGE BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults. BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults (1) Launch Date2008 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
70.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18503564/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10 h |
200 mg 2 times / day unknown, oral dose: 200 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
66% |
200 mg 2 times / day unknown, oral dose: 200 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
RUFINAMIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
3600 mg 2 times / day multiple, oral MTD Dose: 3600 mg, 2 times / day Route: oral Route: multiple Dose: 3600 mg, 2 times / day Sources: |
healthy |
|
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Other AEs: Depression worsened, Suicidal behavior... Other AEs: Depression worsened Sources: Suicidal behavior (serious) Leukopenia (serious) Mood change Central nervous system disorder NOS Hypersensitivity reaction |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Fatigue... Other AEs: QT shortened... AEs leading to discontinuation/dose reduction: Fatigue (1-2) Other AEs:QT shortened (serious) Sources: |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Convulsion, Rash... AEs leading to discontinuation/dose reduction: Convulsion (2%) Sources: Rash (2%) |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Vomiting, Dizziness... AEs leading to discontinuation/dose reduction: Vomiting (1%) Sources: Dizziness (3%) Headache (2%) Nausea (1%) Ataxia (1%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Central nervous system disorder NOS | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
|
| Depression worsened | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
|
| Hypersensitivity reaction | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
|
| Mood change | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
|
| Leukopenia | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Suicidal behavior | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Fatigue | 1-2 Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| QT shortened | serious | 22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Convulsion | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Rash | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Ataxia | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Nausea | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Vomiting | 1% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Headache | 2% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Dizziness | 3% Disc. AE |
22.5 mg/kg 2 times / day multiple, oral Studied dose Dose: 22.5 mg/kg, 2 times / day Route: oral Route: multiple Dose: 22.5 mg/kg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
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/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21, 56 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 56.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21.0 |
weak | yes (co-administration study) Comment: coadministration with triazolam resulted in a 37% decrease in AUC and 23% decrease in Cmax of triazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 21, 56 |
yes [Ki 450 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 20.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021911Orig1s000ClinPharmR_P1.pdf Page: 40, 56 |
no |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 39.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Rufinamide for pediatric patients with Lennox-Gastaut syndrome: a comprehensive overview. | 2011-04-01 |
|
| Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients. | 2010-12-31 |
|
| Ethyl 1-(2,6-difluoro-benz-yl)-1H-1,2,3-triazole-4-carboxyl-ate. | 2010-12-15 |
|
| "Epileptic encephalopathy" of infancy and childhood: electro-clinical pictures and recent understandings. | 2010-12 |
|
| New drugs for pediatric epilepsy. | 2010-12 |
|
| Post-treatment with voltage-gated Na(+) channel blocker attenuates kainic acid-induced apoptosis in rat primary hippocampal neurons. | 2010-12 |
|
| Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells. | 2010-11-23 |
|
| Rufinamide in children and adults with Lennox-Gastaut syndrome: first Italian multicenter experience. | 2010-11 |
|
| Treating Lennox-Gastaut syndrome in epileptic pediatric patients with third-generation rufinamide. | 2010-10-05 |
|
| Antiepileptic drug interactions - principles and clinical implications. | 2010-09 |
|
| Experience with rufinamide in a pediatric population: a single center's experience. | 2010-09 |
|
| Emerging drugs for partial onset seizures. | 2010-09 |
|
| Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study. | 2010-09 |
|
| New antiepileptic drugs: lacosamide, rufinamide, and vigabatrin. | 2010-07 |
|
| Update on anticonvulsant drugs. | 2010-07 |
|
| Rufinamide: a new antiepileptic drug treatment for Lennox-Gastaut syndrome. | 2010-06 |
|
| Severe constipation associated with the use of rufinamide (Banzel) in an adolescent. | 2010-05 |
|
| [Antiepileptic drugs in North America]. | 2010-05 |
|
| Medical management of Lennox-Gastaut syndrome. | 2010-05 |
|
| Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs. | 2010-04 |
|
| Gateways to clinical trials. | 2010-04 |
|
| Rufinamide: a new antiepileptic medication for the treatment of seizures associated with lennox-gastaut syndrome. | 2010-04 |
|
| First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy. | 2010-04 |
|
| Gateways to clinical trials. | 2010-03 |
|
| Stability of extemporaneously prepared rufinamide oral suspensions. | 2010-03 |
|
| Simultaneous HPLC-UV analysis of rufinamide, zonisamide, lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in deproteinized plasma of patients with epilepsy. | 2010-02-01 |
|
| Supporting the recommended paediatric dosing regimen for rufinamide in Lennox-Gastaut syndrome using clinical trial simulation. | 2010-02 |
|
| New Drugs2010, PART 1. | 2010-02 |
|
| A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures. | 2010-02 |
|
| Lennox-Gastaut syndrome: An overview. | 2010-01 |
|
| Rufinamide: a novel broad-spectrum antiepileptic drug. | 2010-01 |
|
| Drug interactions involving the new second- and third-generation antiepileptic drugs. | 2010-01 |
|
| Cost-utility analysis of rufinamide versus topiramate and lamotrigine for the treatment of children with Lennox-Gastaut Syndrome in the United Kingdom. | 2010-01 |
|
| Drug-induced QT interval shortening: potential harbinger of proarrhythmia and regulatory perspectives. | 2010-01 |
|
| The possible antianxiety and mood-stabilizing effects of rufinamide. | 2010 |
|
| The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome in the UK. | 2010 |
|
| Safety and tolerability of rufinamide in children with epilepsy: a pooled analysis of 7 clinical studies. | 2009-12 |
|
| Gateways to clinical trials. | 2009-11 |
|
| Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. | 2009-08 |
|
| Treatment of Lennox-Gastaut syndrome. | 2009-07-08 |
|
| Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care. | 2009-06 |
|
| Truly "rational" polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. | 2009-06 |
|
| Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions. | 2009-06 |
|
| Antiepileptic drug monotherapy: the initial approach in epilepsy management. | 2009-06 |
|
| Adopting an orphan drug: rufinamide for Lennox-Gastaut syndrome. | 2009-05-28 |
|
| New drugs: Febuxostat, lacosamide, and rufinamide. | 2009-05-16 |
|
| Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide. | 2009-04 |
|
| Update on the management of Lennox-Gastaut syndrome with a focus on rufinamide. | 2009 |
|
| Rufinamide: Further evaluation is needed in Lennox-Gastaut syndrome. | 2008-08 |
|
| Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. | 2008-03-02 |
Patents
Sample Use Guides
Starting daily dose: 400-800 mg per day in two equally divided doses. Increase by 400-800 mg every other day until a maximum dose of 3200 mg per day, in two divided doses, is reached.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18503564
In vitro studies with human liver microsomes using con-centrations of rufinamide in the range of 10–300 µmol/L(2.4–72 µg/ml) found no significant inhibition of any ofeight major human CYP isozymes—CYP1A2, CYP2A6,CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, andCYP4A9/11.
| Substance Class |
Chemical
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| Record UNII |
WFW942PR79
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Validated (UNII)
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WHO-ATC |
N03AF03
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NCI_THESAURUS |
C264
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WHO-VATC |
QN03AF03
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LIVERTOX |
NBK548457
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EU-Orphan Drug |
EU/3/04/240
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EMA ASSESSMENT REPORTS |
INOVELON (AUTHORIZED: EPILEPSY)
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FDA ORPHAN DRUG |
193504
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C079703
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7387
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RUFINAMIDE
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106308-44-5
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WFW942PR79
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129228
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7470
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SUB10403MIG
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CHEMBL1201754
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69036
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Rufinamide
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100000089186
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m9696
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1606401
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C75167
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SS-30
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DB06201
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DTXSID1046506
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3534
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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METABOLIC ENZYME -> INHIBITOR |
Ki
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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EXCRETED UNCHANGED |
FECAL; URINE
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METABOLIC ENZYME -> INDUCER |
WEAK
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR |
Shifts hNav1.1 opening to more depolarized voltages without further alterations in the gating properties of hNav1.1, hNav1.2, hNav1.3, and hNav1.6;
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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METABOLITE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> PARENT |
MINOR
URINE
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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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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| Biological Half-life | PHARMACOKINETIC |
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| Volume of Distribution | PHARMACOKINETIC |
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