Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H30O3 |
Molecular Weight | 342.4718 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])C=C(C)C4=CC(=O)CC[C@]34C
InChI
InChIKey=VXIMPSPISRVBPZ-NWUMPJBXSA-N
InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1
Molecular Formula | C22H30O3 |
Molecular Weight | 342.4718 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=23395103
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=23395103
Megestrol acetate is a progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. MEGACE Oral Suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time. But its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes. The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5% to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7% to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%). Megestrol acetate metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. Plasma steady-state pharmacokinetics of megestrol acetate were evaluated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of MEGACE Oral Suspension for 21 days. Plasma concentration data obtained on day 21 were evaluated for up to 48 hours past the last dose.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15086241 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | MEGACE Approved UseMegestrol acetate oral suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Launch Date1993 |
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Palliative | MEGACE Approved UseMegestrol acetate oral suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Launch Date1993 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
753 ng/mL |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
490 ng/mL |
750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1133 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1618 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
1364 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
187 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10476 ng × h/mL |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
6779 ng × h/mL |
750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
12095 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
16268 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
18625 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
8942 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
33.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
39.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
625 mg single, oral dose: 625 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
32.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
31.38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19774117/ |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEGESTROL ACETATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg 2 times / day multiple, oral Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 54-68 years n = 2 Health Status: unhealthy Age Group: 54-68 years Sex: F Population Size: 2 Sources: |
Disc. AE: Osteoporosis... AEs leading to discontinuation/dose reduction: Osteoporosis (2 patients) Sources: |
625 mg 1 times / day multiple, oral Recommended Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: |
unhealthy, 65 years n = 1 Health Status: unhealthy Age Group: 65 years Sex: M Population Size: 1 Sources: |
Disc. AE: Adrenal insufficiency... AEs leading to discontinuation/dose reduction: Adrenal insufficiency (1 patient) Sources: |
40 mg 2 times / day multiple, oral Dose: 40 mg, 2 times / day Route: oral Route: multiple Dose: 40 mg, 2 times / day Sources: |
unhealthy, 85 years n = 1 Health Status: unhealthy Condition: Alzheimer's disease Age Group: 85 years Sex: F Population Size: 1 Sources: |
Disc. AE: Deep vein thrombosis... AEs leading to discontinuation/dose reduction: Deep vein thrombosis (1 patient) Sources: |
400 mg 2 times / day multiple, oral Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Condition: Alzheimer's disease Age Group: 86 years Sex: F Population Size: 1 Sources: |
Disc. AE: Deep vein thrombosis... AEs leading to discontinuation/dose reduction: Deep vein thrombosis (1 patient) Sources: |
1600 mg 1 times / day multiple, oral Highest studied dose Dose: 1600 mg, 1 times / day Route: oral Route: multiple Dose: 1600 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: advanced breast cancer Sex: F Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Osteoporosis | 2 patients Disc. AE |
400 mg 2 times / day multiple, oral Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 54-68 years n = 2 Health Status: unhealthy Age Group: 54-68 years Sex: F Population Size: 2 Sources: |
Adrenal insufficiency | 1 patient Disc. AE |
625 mg 1 times / day multiple, oral Recommended Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: |
unhealthy, 65 years n = 1 Health Status: unhealthy Age Group: 65 years Sex: M Population Size: 1 Sources: |
Deep vein thrombosis | 1 patient Disc. AE |
40 mg 2 times / day multiple, oral Dose: 40 mg, 2 times / day Route: oral Route: multiple Dose: 40 mg, 2 times / day Sources: |
unhealthy, 85 years n = 1 Health Status: unhealthy Condition: Alzheimer's disease Age Group: 85 years Sex: F Population Size: 1 Sources: |
Deep vein thrombosis | 1 patient Disc. AE |
400 mg 2 times / day multiple, oral Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Condition: Alzheimer's disease Age Group: 86 years Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Systemic treatment of hepatocellular carcinoma. | 2001 |
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Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors. | 2001 Apr 6 |
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Treatment. Court decision to allow marketing of generic form of weight-loss drug. | 2001 Aug 3 |
|
Serum immunoglobulins, total protein and albumin levels during UniplantR use by Nigerian women. | 2001 Dec |
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Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). | 2001 Feb |
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Cost-effectiveness analysis of exemestane compared with megestrol in patients with advanced breast carcinoma. | 2001 Feb 1 |
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Inhibitory effect of nomegestrol acetate on steroidogenesis of cultured granulosa cells from rat ovary in vitro. | 2001 Jan |
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Megestrol treatment in patients with hepatocellular carcinoma. | 2001 Nov 16 |
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Variant estrogen receptors and their role in liver disease. | 2002 Jul 31 |
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Effect of megestrol caproate on the reproductive function of laboratory animals. | 2002 Jun |
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Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. | 2002 Oct 29 |
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Phase I and pharmacokinetic study of vinblastine and high-dose megestrol acetate. | 2002 Sep |
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Acute effects of megestrol on the hypothalamic-pituitary-adrenal axis. | 2003 Dec |
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Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy. | 2003 Jul 25 |
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Economic evaluation of antiaromatase agents in the second-line treatment of metastatic breast cancer. | 2003 Nov |
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The role of MRI in the conservative management of endometrial cancer. | 2004 Apr |
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A comparison of the central effects of different progestins used in hormone replacement therapy. | 2004 Aug 20 |
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Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy. | 2004 Jul-Aug |
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Cost utility and budget impact of third-generation aromatase inhibitors for advanced breast cancer: a literature-based model analysis of costs in the Italian National Health Service. | 2004 Sep |
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Treatment with inhibitors of angiogenesis in advanced hepatocellular carcinoma: a new tool in our hands or simply a hope? | 2005 Apr |
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The effects of aromatase inhibitors on lipids and thrombosis. | 2005 Aug |
|
[Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate]. | 2005 Feb |
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Hormonal treatment of a recurrent granulosa cell tumor of the ovary: case report and review of the literature. | 2005 Mar |
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Review of cost-effectiveness analyses in hormonal therapies in advanced breast cancer. | 2005 Sep |
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Letrozole: a pharmacoeconomic review of its use in postmenopausal women with breast cancer. | 2006 |
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Megestrol attenuates the hormonal response to CCK-4-induced panic attacks. | 2006 |
|
Hepatocellular carcinoma--Pathological complete response to oral capecitabine, megestrol and thalidomide. | 2006 |
|
Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year. | 2006 Dec |
|
Nanoparticles of poorly water-soluble drugs prepared by supercritical fluid extraction of emulsions. | 2006 Jan |
|
A successful live birth through in vitro fertilization program after conservative treatment of FIGO grade I endometrial cancer. | 2006 Jun |
|
Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials. | 2006 Jun 19 |
|
Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimenopausal women. | 2006 Mar-Apr |
|
[Pharmacological therapy of cancer anorexia-cachexia]. | 2006 May |
|
Activation of nitric oxide synthesis in human endothelial cells using nomegestrol acetate. | 2006 Oct |
|
Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. | 2007 Feb |
|
Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women. | 2007 May-Jun |
Patents
Sample Use Guides
Oral Suspension is 800 mg/day (20 mL/day).
In clinical trials evaluating different dose schedules, daily doses of 400 and 800 mg/day.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15297426
Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC (50) of 260 uM (24-h incubation)
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 14:58:15 GMT 2023
by
admin
on
Fri Dec 15 14:58:15 GMT 2023
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Record UNII |
EA6LD1M70M
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Record Status |
Validated (UNII)
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Record Version |
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Official 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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Brand Name | English | ||
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Common Name | English |
Classification Tree | Code System | Code | ||
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WHO-VATC |
QG03AC05
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WHO-ATC |
G03AC05
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LIVERTOX |
593
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WHO-ATC |
G03FB04
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CFR |
21 CFR 520.1341
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NCI_THESAURUS |
C776
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WHO-VATC |
QG03DB02
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WHO-ATC |
G03FA08
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WHO-ATC |
L02AB01
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WHO-VATC |
QG03FA08
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WHO-ATC |
G03AB01
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WHO-VATC |
QG03AB01
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NDF-RT |
N0000175602
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WHO-ATC |
G03DB02
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WHO-VATC |
QL02AB01
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NDF-RT |
N0000011301
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WHO-VATC |
QG03FB04
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WHO-ATC |
G03AA04
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WHO-VATC |
QG03AA04
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EA6LD1M70M
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1529
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C630
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6722
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6703
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3233
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EA6LD1M70M
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CHEMBL1201139
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MEGESTROL
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3562-63-8
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SUB08712MIG
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19090
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DTXSID00100933
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222-628-6
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100000081461
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D008535
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Elimination PHARMACOKINETIC PHARMACOKINETIC |
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