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Identification
NameMegestrol acetate
Accession NumberDB00351  (APRD01092)
Typesmall molecule
Groupsapproved
Description

17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. 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. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
17-Acetoxy-6-methylpregna-4,6-diene-3,20-dioneNot AvailableNot Available
17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione 17-acetateNot AvailableNot Available
17α-Acetoxy-6-dehydro-6-methylprogesteroneNot AvailableNot Available
17α-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetateNot AvailableNot Available
6-Dehydro-6-methyl-17α-acetoxyprogesteroneNot AvailableNot Available
6-Methyl-17α-acetoxypregna-4,6-diene-3,20-dioneNot AvailableNot Available
6-Methyl-17α-hydroxy-delta(sup 6)-progesterone acetateNot AvailableNot Available
6-Methyl-6-dehydro-17α-acetoxyprogesteroneNot AvailableNot Available
6-Methyl-delta(sup 4,6)-pregnadien-17α-ol-3,20-dione acetateNot AvailableNot Available
6-Methyl-delta(sup 6)-dehydro-17α-acetoxyprogesteroneNot AvailableNot Available
MGANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MaygaceNot Available
MegaceNot Available
Megace ESNot Available
MegestilNot Available
Brand mixturesNot Available
Categories
CAS number595-33-5
WeightAverage: 370.4819
Monoisotopic: 370.214409448
Chemical FormulaC23H30O4
InChI KeyURXWVWVPMJSAJD-KOORYGTMSA-N
InChI
InChI=1S/C23H30O4/c1-14(24)23(27-15(2)25)12-9-20-18-6-5-16-13-17(26)7-10-21(16,3)19(18)8-11-22(20,23)4/h5-6,13,18-20H,7-12H2,1-4H3/t18-,19+,20+,21+,22+,23+/m1/s1
IUPAC Name
(1S,2R,10R,11S,14R,15S)-14-acetyl-2,15-dimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-6,8-dien-14-yl acetate
SMILES
[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=CC2=CC(=O)CC[C@]12C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsSteroid Esters; Ketosteroids; Ketones; Carboxylic Acid Esters; Ethers; Enolates; Polyamines
Substituents20-keto-steroid; 3-keto-steroid; carboxylic acid ester; ketone; enolate; ether; polyamine; carboxylic acid derivative; carbonyl group
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
Pharmacology
IndicationFor the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries.
PharmacodynamicsMegestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.
Mechanism of actionThe 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.
AbsorptionVariable, but well absorbed orally.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic. Megestrol 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. No active metabolites have been identified.

Route of eliminationThe major route of drug elimination in humans is urine. 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.
Half life34 hours
ClearanceNot Available
ToxicityNo serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362].
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9959
Blood Brain Barrier + 0.9617
Caco-2 permeable + 0.651
P-glycoprotein substrate Substrate 0.6107
P-glycoprotein inhibitor I Inhibitor 0.9149
P-glycoprotein inhibitor II Inhibitor 0.7016
Renal organic cation transporter Non-inhibitor 0.7753
CYP450 2C9 substrate Non-substrate 0.8642
CYP450 2D6 substrate Non-substrate 0.908
CYP450 3A4 substrate Substrate 0.7744
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.8907
CYP450 2D6 substrate Non-inhibitor 0.9532
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8095
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.899
Ames test Non AMES toxic 0.9775
Carcinogenicity Non-carcinogens 0.9273
Biodegradation Not ready biodegradable 0.9354
Rat acute toxicity 1.8121 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9429
hERG inhibition (predictor II) Non-inhibitor 0.7761
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
  • Par pharmaceutical inc
  • Apotex inc richmond hill
  • Roxane laboratories inc
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
  • Barr laboratories inc
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
Packagers
Dosage forms
FormRouteStrength
SuspensionOral
TabletOral
Prices
Unit descriptionCostUnit
Megestrol Acetate 40 mg/ml Suspension 480ml Bottle297.92USDbottle
Megestrol Acetate 40 mg/ml Suspension 240ml Bottle149.71USDbottle
Megestrol acetate powder30.6USDg
Megestrol 40 mg tablet1.17USDtablet
Megestrol Acetate 40 mg tablet1.15USDtablet
Megestrol Acetate 20 mg tablet0.72USDtablet
Megace 40 mg/ml oral suspension0.71USDml
Megestrol 20 mg tablet0.65USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States71015762004-04-222024-04-22
United States51456841994-01-252011-01-25
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point218.0-220.0 °CNot Available
water solubility2 µg/mL (at 37 °C for the acetate salt)Not Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
water solubility3.38e-03 g/lALOGPS
logP2.99ALOGPS
logP3.48ChemAxon
logS-5ALOGPS
pKa (strongest acidic)17.83ChemAxon
pKa (strongest basic)-4.8ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count0ChemAxon
polar surface area60.44ChemAxon
rotatable bond count3ChemAxon
refractivity104.37ChemAxon
polarizability41.33ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Klaus ANNEN, Thomas Linz, Karl-Heinz Neff, Rolf Bohlmann, Henry Laurent, “PROCESS FOR PREPARING 17ALPHA-ACETOXY-6-METHYLENEPREGN-4-ENE-3,20-DIONE, MEDROXYPROGESTERONE ACETATE AND MEGESTROL ACETATE.” U.S. Patent US20090012321, issued January 08, 2009.

US20090012321
General Reference
  1. Berenstein EG, Ortiz Z: Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310. Pubmed
  2. Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M: Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9. Pubmed
  3. Rao GG, Miller DS: Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. Pubmed
  4. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. Pubmed
  5. Orme LM, Bond JD, Humphrey MS, Zacharin MR, Downie PA, Jamsen KM, Mitchell SL, Robinson JM, Grapsas NA, Ashley DM: Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003 Jul 15;98(2):397-405. Pubmed
External Links
ResourceLink
KEGG DrugD00952
KEGG CompoundC08151
ChEBI6723
ChEMBLCHEMBL1201139
Therapeutic Targets DatabaseDAP000861
PharmGKBPA450351
Drug Product Database2223112
RxListhttp://www.rxlist.com/cgi/generic4/megace_es.htm
Drugs.comhttp://www.drugs.com/cdi/megestrol.html
WikipediaMegestrol
ATC CodesG03DB04G03AC05G03DB02L02AB01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelshow(278 KB)
MSDSshow(71.9 KB)
Interactions
Drug Interactions
Drug
AmobarbitalThe enzyme inducer, amobarbital, decreases the effect of the hormone agent, megestrol.
AprobarbitalThe enzyme inducer, aprobarbital, decreases the effect of the hormone agent, megestrol.
ButabarbitalThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, megestrol.
ButalbitalThe enzyme inducer, butalbital, decreases the effect of the hormone agent, megestrol.
ButethalThe enzyme inducer, butethal, decreases the effect of the hormone agent, megestrol.
EthotoinThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, megestrol.
FosphenytoinThe enzyme inducer, fosphenytoin, may decrease the effect of the hormone, megestrol.
GriseofulvinThe enzyme inducer, griseofulvin, may decrease the effect of the hormone, megestrol.
HeptabarbitalThe enzyme inducer, heptabarbital, decreases the effect of the hormone agent, megestrol.
HexobarbitalThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, megestrol.
MephenytoinThe enzyme inducer, mephenytoin, decreases the effect of the hormone agent, megestrol.
MethohexitalThe enzyme inducer, methohexital, decreases the effect of the hormone agent, megestrol.
MethylphenobarbitalThe enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, megestrol.
PentobarbitalThe enzyme inducer, pentobarbital, decreases the effect of the hormone agent, megestrol.
PhenobarbitalThe enzyme inducer, phenobarbital, may decrease the effect of the hormone, megestrol.
PhenytoinThe enzyme inducer, phenytoin, may decrease the effect of megestrol.
PrimidoneThe enzyme inducer, primidone, may decrease the effect of the hormone, megestrol.
SecobarbitalThe enzyme inducer, secobarbital, decreases the effect of the hormone agent, megestrol.
TalbutalThe enzyme inducer, talbutal, decreases the effect of the hormone agent, megestrol.
Food Interactions
  • Take with food.

Targets

1. Progesterone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Progesterone receptor P06401 Details

References:

  1. Vadivelu S, Sharer L, Schulder M: Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy. J Neurosurg. 2010 May;112(5):920-4. Pubmed
  2. Mokbel K: Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8. Pubmed
  3. Wentling GK, Sevin BU, Geiger XJ, Bridges MD: Benign metastasizing leiomyoma responsive to megestrol: case report and review of the literature. Int J Gynecol Cancer. 2005 Nov-Dec;15(6):1213-7. Pubmed
  4. Gruber T, Dare AO, Balos LL, Lele S, Fenstermaker RA: Multiple meningiomas arising during long-term therapy with the progesterone agonist megestrol acetate. Case report. J Neurosurg. 2004 Feb;100(2):328-31. Pubmed
  5. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. Pubmed
  6. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. Pubmed
  7. Wiedemann K, Hirschmann M, Knaudt K, Rupprecht R, Seier FE, Holsboer F: Sleep endocrine effects of megestrol acetate in healthy men. J Neuroendocrinol. 1998 Sep;10(9):719-27. Pubmed
  8. Lamberts SW, Uitterlinden P, Bons EG, Verleun T: Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. Cancer Res. 1985 Mar;45(3):1015-9. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

  1. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. Pubmed
  2. Gonzalez Villarroel P, Fernandez Perez I, Paramo C, Gentil Gonzalez M, Carnero Lopez B, Vazquez Tunas ML, Carrasco Alvarez JA: Megestrol acetate-induced adrenal insufficiency. Clin Transl Oncol. 2008 Apr;10(4):235-7. Pubmed
  3. Wiedemann K, Hirschmann M, Knaudt K, Rupprecht R, Seier FE, Holsboer F: Sleep endocrine effects of megestrol acetate in healthy men. J Neuroendocrinol. 1998 Sep;10(9):719-27. Pubmed
  4. Chao Y, Chan WK, Wang SS, Lai KH, Chi CW, Lin CY, Chan A, Whang-Peng J, Lui WY, Lee SD: Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997 Apr;12(4):277-81. Pubmed
  5. Lamberts SW, Uitterlinden P, Bons EG, Verleun T: Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. Cancer Res. 1985 Mar;45(3):1015-9. Pubmed
  6. Kontula K, Paavonen T, Luukkainen T, Andersson LC: Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes. Biochem Pharmacol. 1983 May 1;32(9):1511-8. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Wang L, Yang CP, Horwitz SB, Trail PA, Casazza AM: Reversal of the human and murine multidrug-resistance phenotype with megestrol acetate. Cancer Chemother Pharmacol. 1994;34(2):96-102. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09