Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C9H13N3O5 |
Molecular Weight | 243.2166 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(=O)N(C=C1)[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O
InChI
InChIKey=UHDGCWIWMRVCDJ-CCXZUQQUSA-N
InChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1
Molecular Formula | C9H13N3O5 |
Molecular Weight | 243.2166 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021041s023lbl.pdfCurator's Comment: Description was created using several sources including:
http://www.ebi.ac.uk/chebi/searchId.do?chebiId=28680
http://www.tandfonline.com/doi/abs/10.1517/17425247.2010.527330
Sources: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021041s023lbl.pdf
Curator's Comment: Description was created using several sources including:
http://www.ebi.ac.uk/chebi/searchId.do?chebiId=28680
http://www.tandfonline.com/doi/abs/10.1517/17425247.2010.527330
Cytarabine is a pyrimidine nucleoside analog. Cytarabine or cytosine arabinoside (Cytosar-U or Depocyt) is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma. It also has antiviral and immunosuppressant properties. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. It is a cell cycle phase-specific, affecting cells only during the S phase of cell division. Intracellularly, cytarabine is converted into cytarabine-5-triphosphate (ara-CTP), which is the active metabolite. The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA polymerase. Incorporation into DNA and RNA may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture.The drug has a short plasma half-life, low stability and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been explored extensively to enhance the half-life, stability and delivery of cytarabine. Alternative, delivery systems of cytarabine have emerged for the treatment of different cancers. The liposomal-cytarabine formulation has been approved for the treatment of lymphomatous meningitis.
CNS Activity
Originator
Sources: https://en.wikipedia.org/wiki/Cytarabine
Curator's Comment: Cytarabine was first synthesized in 1959 by Richard Walwick, Walden Roberts, and Charles Dekker at the University of California, Berkeley. It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in the U.S. by Upjohn under the trade name Cytosar-U and is at present manufactured by Pfizer, Sicor Pharmaceuticals and Teva. CYTOSAR (cytarabine injection) was developed in September 1994 Dana-Farber Cancer Institute and is manufactured by Pfizer and Perrigo. DEPOCYT - (cytarabine injection, lipid complex) manufactured by Manufactured by: Pacira Pharmaceuticals Inc., distributed by Sigma-Tau Pharmaceutical, Inc. is an intrathecal cancer chemotherapeutic agent approved by FDA is used for the treatment of lymphomatous meningitis.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL5367 Sources: http://www.drugbank.ca/drugs/DB00987 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Sources: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021041s023lbl.pdf |
Primary | CYTARABINE Approved UseCytarabine in combination with other approved anticancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and children. It has also been found useful in the treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. Intrathecal administration of cytarabine injection (preservative-free only) is indicated for the prophylaxis and treatment of meningeal leukemia. Launch Date1969 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
62.2 μg/mL |
100 mg/m² 1 times / day multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: DAUNORUBICIN |
CYTARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1900 μg × h/mL |
100 mg/m² 1 times / day multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: DAUNORUBICIN |
CYTARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
40.4 h |
100 mg/m² 1 times / day multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: DAUNORUBICIN |
CYTARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
80 h |
50 mg single, intrathecal dose: 50 mg route of administration: Intrathecal experiment type: SINGLE co-administered: |
CYTARABINE unknown | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.363, 366 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.363, 366 |
Disc. AE: Cerebellar disorder NOS, Diarrhea... AEs leading to discontinuation/dose reduction: Cerebellar disorder NOS (grade 4, 66.7%) Sources: Page: p.363, 366Diarrhea (grade 3, 66.7%) |
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.2578 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.2578 |
Disc. AE: Cerebellar disorder NOS, Cerebellar disorder NOS... AEs leading to discontinuation/dose reduction: Cerebellar disorder NOS (grade 4, 33.3%) Sources: Page: p.2578Cerebellar disorder NOS (grade 5, 16.7%) |
3 g/m2 2 times / day multiple, intravenous MTD Dose: 3 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 3 g/m2, 2 times / day Sources: Page: p.366 |
unhealthy, 16-76 n = 27 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 27 Sources: Page: p.366 |
|
100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Disc. AE: Bone marrow depression, Leukopenia... AEs leading to discontinuation/dose reduction: Bone marrow depression Sources: Page: p.1Leukopenia Thrombocytopenia Anemia Nausea Vomiting Diarrhea Abdominal pain Oral ulceration Hepatic dysfunction NOS |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | grade 3, 66.7% Disc. AE |
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.363, 366 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.363, 366 |
Cerebellar disorder NOS | grade 4, 66.7% Disc. AE |
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.363, 366 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.363, 366 |
Cerebellar disorder NOS | grade 4, 33.3% Disc. AE |
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.2578 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.2578 |
Cerebellar disorder NOS | grade 5, 16.7% Disc. AE |
4.5 g/m2 2 times / day multiple, intravenous Highest studied dose Dose: 4.5 g/m2, 2 times / day Route: intravenous Route: multiple Dose: 4.5 g/m2, 2 times / day Sources: Page: p.2578 |
unhealthy, 16-76 n = 6 Health Status: unhealthy Condition: Acute leukemia Age Group: 16-76 Sex: M+F Population Size: 6 Sources: Page: p.2578 |
Abdominal pain | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Anemia | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Bone marrow depression | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Diarrhea | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Hepatic dysfunction NOS | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Leukopenia | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Nausea | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Oral ulceration | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Thrombocytopenia | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Vomiting | Disc. AE | 100 mg/m2 1 times / day multiple, intravenous Recommended Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute non-lymphocytic leukemia Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/ Page: 4.0 |
yes [IC50 6.6 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/15204103/ Page: 4.0 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Protection by short-chain fatty acids against 1-beta-D-arabinofuranosylcytosine-induced intestinal lesions in germfree mice. | 1999 Apr |
|
[Topotecan: a new field of use]. | 1999 Nov-Dec |
|
Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. | 2000 Jan-Feb |
|
Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. | 2000 May |
|
Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. | 2001 Apr |
|
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts. | 2001 Apr |
|
The neuron-glia signal beta-neuregulin promotes Schwann cell motility via the MAPK pathway. | 2001 Apr 1 |
|
Parotid mucoepidermoid carcinoma following chemotherapy for childhood acute lymphoblastic leukemia. | 2001 Apr-May |
|
Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism. | 2001 Feb |
|
Survival in patients with intermediate or high grade non-Hodgkin's lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP. | 2001 Feb 2 |
|
Cyclosporin increases cellular idarubicin and idarubicinol concentrations in relapsed or refractory AML mainly due to reduced systemic clearance. | 2001 Jan |
|
Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. | 2001 Jan |
|
PBPC mobilization with chemotherapy and G-CSF in patients with chronic myeloid leukemia: quantification of bcr/abl-positive cells by interphase fluorescence in situ hybridization and competitive PCR. | 2001 Jan |
|
Blasts from elderly acute myeloid leukemia patients are characterized by low levels of culture- and drug-induced apoptosis. | 2001 Jan |
|
Primary central nervous system lymphoma 1991-1997: outcome and late adverse effects after combined modality treatment. | 2001 Jan 1 |
|
Porcine Choroid plexus epithelial cells in culture: regulation of barrier properties and transport processes. | 2001 Jan 1 |
|
Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study. | 2001 Jan 3 |
|
Results of IDA-FLAG programme in the treatment of recurrent acute myeloblastic leukaemia--preliminary report. | 2001 Jan-Feb |
|
Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside. | 2001 Jan-Feb |
|
Neutrophilic eccrine hidradenitis in two neutropaenic patients. | 2001 Mar |
|
Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials. | 2001 Mar |
|
Combination chemotherapy utilizing continuous infusion of intermediate-dose cytarabine for refractory or recurrent acute myeloid leukemia. | 2001 Mar |
Sample Use Guides
Induction therapy: DepoCyt (cytarabine liposome injection), 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 14 days for 2 doses (weeks 1 and 3).
Consolidation therapy: DepoCyt, 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 14 days for 3 doses (weeks 5, 7 and 9) followed by 1 additional dose at week 13.
Maintenance: DepoCyt, 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 28 days for 4 doses (weeks 17, 21, 25 and 29).
Route of Administration:
Intratracheal
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/24527217
Curator's Comment: The effect of Ara-C (0.1 μM) treatment on HUVEC proliferation alone or in drug combinations compared to drug-free control cultures. Results are expressed as mean percentage ± SEM from three independent experiments (six replicates per condition) relative to corresponding untreated control cultures.
Human umbilical vein endothelial cells (HUVECs) and human osteosarcoma cell line (Cal72) were incubated with various concentrations of Cytarabine (Ara-C) (0.01–20 μM) for 3 days
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 16:40:24 GMT 2023
by
admin
on
Sat Dec 16 16:40:24 GMT 2023
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Record UNII |
04079A1RDZ
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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 |
L01XY01
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FDA ORPHAN DRUG |
234806
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NDF-RT |
N0000175595
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NDF-RT |
N0000000233
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EMA ASSESSMENT REPORTS |
DEPOCYT (AUTHORIZED: MENINGEAL NEOPLASMS)
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FDA ORPHAN DRUG |
265808
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NCI_THESAURUS |
C1557
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WHO-ESSENTIAL MEDICINES LIST |
8.2
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FDA ORPHAN DRUG |
73393
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LIVERTOX |
NBK548291
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WHO-ATC |
L01BC01
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EU-Orphan Drug |
EU/3/11/942
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WHO-VATC |
QL01BC01
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968804
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ALTERNATIVE | |||
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205-705-9
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PRIMARY | |||
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DTXSID3022877
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DB00987
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SUB06880MIG
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C408
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3041
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04079A1RDZ
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m4051
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PRIMARY | Merck Index | ||
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6253
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PRIMARY | |||
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CYTARABINE
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CHEMBL803
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1162002
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04079A1RDZ
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4827
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770
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147-94-4
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D003561
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28680
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100000089874
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1709
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3049
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287459
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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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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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