You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMedroxyprogesterone Acetate
Accession NumberDB00603  (APRD00627)
Typesmall molecule
Groupsapproved, investigational
Description

Medroxyprogesterone acetate (INN, USAN, BAN), also known as 17α-hydroxy-6α-methylprogesterone acetate, and commonly abbreviated as MPA, is a steroidal progestin, a synthetic variant of the human hormone progesterone. It is used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis as well as several other indications.
MPA is a more potent derivative of its parent compound medroxyprogesterone (MP). While medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, what is normally being administered is MPA and not MP. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(6alpha)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dioneNot AvailableNot Available
17-Acetoxy-6alpha-methylprogesteroneNot AvailableNot Available
17-Acetoxy-6α-methylprogesteroneNot AvailableNot Available
17alpha-Hydroxy-6alpha-methylprogesterone acetateNot AvailableNot Available
17α-hydroxy-6α-methylprogesterone acetateNot AvailableNot Available
6-alpha-Methyl-17-alpha-acetoxyprogesteroneNot AvailableNot Available
6-alpha-Methyl-17-alpha-hydroxyprogesterone acetateNot AvailableNot Available
6alpha-Methyl-17-acetoxy progesteroneNot AvailableNot Available
6alpha-Methyl-17alpha-hydroxyprogesterone acetateNot AvailableNot Available
6alpha-Methyl-4-pregnene-3,20-dion-17alpha-ol acetateNot AvailableNot Available
6α-Methyl-17-acetoxy progesteroneNot AvailableNot Available
6α-Methyl-17α-hydroxyprogesterone acetateNot AvailableNot Available
Medroxyacetate progesteroneNot AvailableNot Available
Medroxyprogesterone 17-acetateNot AvailableNot Available
Medroxyprogesterone acetateNot AvailableNot Available
MethylacetoxyprogesteroneNot AvailableNot Available
MetigestronaNot AvailableNot Available
MPANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Depo-proveraNot Available
Depo-subq provera 104Not Available
MakenaNot Available
ProveraNot Available
Brand mixtures
Brand NameIngredients
LunelleMedroxyprogesterone acetate + Estradiol
Categories
CAS number71-58-9
WeightAverage: 386.5244
Monoisotopic: 386.245709576
Chemical FormulaC24H34O4
InChI KeyPSGAAPLEWMOORI-PEINSRQWSA-N
InChI
InChI=1S/C24H34O4/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26/h13-14,18-20H,6-12H2,1-5H3/t14-,18+,19-,20-,22+,23-,24-/m0/s1
IUPAC Name
(1S,2R,8S,10R,11S,14R,15S)-14-acetyl-2,8,15-trimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-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[C@H](C)C2=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
IndicationUsed as a contraceptive and to treat secondary amenorrhea, abnormal uterine bleeding, pain associated with endometriosis, endometrial and renal cell carcinomas, paraphilia in males, GnRH-dependent forms of precocious puberty, as well as to prevent endometrial changes associated with estrogens.
PharmacodynamicsMedroxyprogesterone acetate is a synthetic progestin more potent than progesterone.
Mechanism of actionProgestins diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.
AbsorptionRapidly absorbed from GI tract
Volume of distributionNot Available
Protein binding90%
Metabolism

Hepatic

SubstrateEnzymesProduct
Medroxyprogesterone Acetate
6β-HydroxymedroxyprogesteroneDetails
Medroxyprogesterone Acetate
2β-HydroxymedroxyprogesteroneDetails
Medroxyprogesterone Acetate
1β-HydroxymedroxyprogesteroneDetails
Route of eliminationFollowing oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
Half life50 days
Clearance
  • 64110 +/- 42662 mL/min [postmenopausal women under fasting conditions with a single Dose of 2 × 10 mg]
  • 74123 +/- 35126 mL/min [postmenopausal women under fasting conditions with a single Dose of 8 × 2.5 mg]
  • 41963 +/- 38402 mL/min [postmenopausal women following daily administration of one PROVERA 10 mg tablet for 7 days]
ToxicitySide effects include loss of bone mineral density, BMD changes in adult women, bleeding irregularities, cancer risks, and thromboembolic disorders.
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
  • Sandoz canada inc
  • Teva parenteral medicines inc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Usl pharma inc
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
SuspensionIntramuscular
TabletOral
Prices
Unit descriptionCostUnit
Depo-Provera 400 mg/ml Suspension 2.5ml Vial201.13USDvial
Depo-subq provera 104 syringe108.17USDsyringe
Depo-provera 400 mg/ml vial96.7USDml
Depo-Provera 150 mg/ml Suspension 1ml Syringe94.58USDsyringe
MedroxyPROGESTERone Acetate 150 mg/ml Suspension 1ml Syringe60.56USDsyringe
MedroxyPROGESTERone Acetate 150 mg/ml Suspension 1ml Vial55.17USDvial
Depo-Provera 150 mg/ml31.02USDml
Medroxyprogesterone Acetate 150 mg/ml23.05USDml
Medroxyprogesterone ace powder18.97USDg
Depo-Provera 50 mg/ml6.01USDml
Provera 10 mg tablet2.03USDtablet
Provera 5 mg tablet1.57USDtablet
Provera 100 mg Tablet1.41USDtablet
Provera 2.5 mg tablet1.15USDtablet
Apo-Medroxy 100 mg Tablet0.96USDtablet
Provera 10 mg Tablet0.73USDtablet
MedroxyPROGESTERone Acetate 10 mg tablet0.51USDtablet
MedroxyPROGESTERone Acetate 5 mg tablet0.48USDtablet
MedroxyPROGESTERone Acetate 2.5 mg tablet0.43USDtablet
Medroxyprogesterone 10 mg tablet0.4USDtablet
Provera 5 mg Tablet0.36USDtablet
Medroxyprogesterone 5 mg tablet0.33USDtablet
Apo-Medroxy 10 mg Tablet0.33USDtablet
Novo-Medrone 10 mg Tablet0.33USDtablet
Medroxyprogesterone 2.5 mg tablet0.32USDtablet
Provera 2.5 mg Tablet0.18USDtablet
Apo-Medroxy 5 mg Tablet0.16USDtablet
Novo-Medrone 5 mg Tablet0.16USDtablet
Apo-Medroxy 2.5 mg Tablet0.08USDtablet
Novo-Medrone 2.5 mg Tablet0.08USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada24090592006-04-182021-04-25
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point214.5 °CPhysProp
water solubility22.2mg/LNot Available
logP3.5Not Available
Predicted Properties
PropertyValueSource
water solubility2.21e-03 g/lALOGPS
logP3.42ALOGPS
logP4.13ChemAxon
logS-5.2ALOGPS
pKa (strongest acidic)17.82ChemAxon
pKa (strongest basic)-4.9ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count0ChemAxon
polar surface area60.44ChemAxon
rotatable bond count3ChemAxon
refractivity107.81ChemAxon
polarizability44.05ChemAxon
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. 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
  2. Lenco W, Mcknight M, Macdonald AS: Effects of cortisone acetate, methylprednisolone and medroxyprogesterone on wound contracture and epithelization in rabbits. Ann Surg. 1975 Jan;181(1):67-73. Pubmed
External Links
ResourceLink
KEGG DrugD00951
KEGG CompoundC08150
ChEBI6715
ChEMBLCHEMBL717
Therapeutic Targets DatabaseDAP001211
PharmGKBPA450344
IUPHAR2879
Guide to Pharmacology2879
Drug Product Database2247583
RxListhttp://www.rxlist.com/cgi/generic/medrox.htm
Drugs.comhttp://www.drugs.com/medroxyprogesterone.html
WikipediaMedroxyprogesterone
ATC CodesNot Available
AHFS Codes
  • 68:32.00
PDB EntriesNot Available
FDA labelshow(1.2 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolMedroxyprogesterone may increase the anticoagulant effect of acenocoumarol.
AmobarbitalThe enzyme inducer, amobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
AnisindioneMedroxyprogesterone may increase the anticoagulant effect of anisindione.
AprobarbitalThe enzyme inducer, aprobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
ArtemetherArtemether may decrease the effectiveness of medroxyprogesterone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
BexaroteneBexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of medroxyprogesterone, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).
BosentanBosentan may decrease the contraceptive effect of medroxyprogesterone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.
ButabarbitalThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, medroxyprogesterone.
ButalbitalThe enzyme inducer, butalbital, decreases the effect of the hormone agent, medroxyprogesterone.
ButethalThe enzyme inducer, butethal, decreases the effect of the hormone agent, medroxyprogesterone.
ColesevelamBile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.
DicoumarolMedroxyprogesterone may increase the anticoagulant effect of dicumarol.
EthotoinThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, medroxyprogesterone.
FosphenytoinThe enzyme inducer, fosphenytoin, may decrease the effect of the hormone, medroxyprogesterone.
GriseofulvinThe enzyme inducer, griseofulvin, may decrease the effect of the hormone, medroxyprogesterone.
HeptabarbitalThe enzyme inducer, heptabarbital, decreases the effect of the hormone agent, medroxyprogesterone.
HexobarbitalThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
MephenytoinThe enzyme inducer, mephenytoin, decreases the effect of the hormone agent, medroxyprogesterone.
MethohexitalThe enzyme inducer, methohexital, decreases the effect of the hormone agent, medroxyprogesterone.
MethylphenobarbitalThe enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
PentobarbitalThe enzyme inducer, pentobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
PhenobarbitalThe enzyme inducer, phenobarbital, may decrease the effect of the hormone, medroxyprogesterone.
PhenytoinThe enzyme inducer, phenytoin, may decrease the effect of medroxyprogesterone.
PrimidoneThe enzyme inducer, primidone, may decrease the effect of the hormone, medroxyprogesterone.
SecobarbitalThe enzyme inducer, secobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
TalbutalThe enzyme inducer, talbutal, decreases the effect of the hormone agent, medroxyprogesterone.
ThiopentalThiopental may decrease the effect of Medroxyprogesterone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.
WarfarinMedroxyprogesterone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if medroxyprogesterone is initiated, discontinued or dose changed.
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. Risch HA, Bale AE, Beck PA, Zheng W: PGR +331 A/G and increased risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1738-41. Pubmed
  2. Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. Pubmed
  3. Gizard F, Robillard R, Gross B, Barbier O, Revillion F, Peyrat JP, Torpier G, Hum DW, Staels B: TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. Mol Cell Biol. 2006 Oct;26(20):7632-44. Pubmed
  4. Wu HB, Fabian S, Jenab S, Quinones-Jenab V: Progesterone receptors activation after acute cocaine administration. Brain Res. 2006 Dec 18;1126(1):188-92. Epub 2006 Nov 15. Pubmed
  5. Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP: The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol. 2007 Feb;21(2):359-75. Epub 2006 Nov 30. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Estrogen receptor P03372 Details

References:

  1. Jain JK, Li A, Yang W, Minoo P, Felix JC: Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate. Fertil Steril. 2007 Jan;87(1):8-23. Epub 2006 Nov 7. Pubmed
  2. Kumar AS, Cureton E, Shim V, Sakata T, Moore DH, Benz CC, Esserman LJ, Hwang ES: Type and duration of exogenous hormone use affects breast cancer histology. Ann Surg Oncol. 2007 Feb;14(2):695-703. Epub 2006 Nov 14. Pubmed
  3. Lessey BA, Palomino WA, Apparao K, Young SL, Lininger RA: Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S9. Pubmed
  4. Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubura A: Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. In Vivo. 2006 Nov-Dec;20(6B):829-36. Pubmed
  5. Ghebeh H, Tulbah A, Mohammed S, Elkum N, Bin Amer SM, Al-Tweigeri T, Dermime S: Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells. Int J Cancer. 2007 Aug 15;121(4):751-8. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhang JW, Liu Y, Zhao JY, Wang LM, Ge GB, Gao Y, Li W, Liu HT, Liu HX, Zhang YY, Sun J, Yang L: Metabolic profiling and cytochrome P450 reaction phenotyping of medroxyprogesterone acetate. Drug Metab Dispos. 2008 Nov;36(11):2292-8. Epub 2008 Aug 25. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 P26439 Details

References:

  1. Lee TC, Miller WL, Auchus RJ: Medroxyprogesterone acetate and dexamethasone are competitive inhibitors of different human steroidogenic enzymes. J Clin Endocrinol Metab. 1999 Jun;84(6):2104-10. Pubmed

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11