Identification

Name
Drospirenone
Accession Number
DB01395
Type
Small Molecule
Groups
Approved
Description

Drospirenone is a synthetic progestin that is an analog to spironolactone. It is found in a number of birth control formulations. Drospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone. As such it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic. It was shown in animal studies that drospirenone exhibits antiandrogenic activity judging from accessory sex gland growth in castrated, androgen-treated, juvenile rats.

Structure
Thumb
Synonyms
  • 1,2-Dihydrospirorenone
  • 6beta,7Beta;15beta,16beta-dimethylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone
  • 6β,7β,15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17 carbolactone
  • Dehydrospirorenone
  • Drospirenona
  • Drospirenone
  • Drospirenonum
  • DRSP
External IDs
ZK-30595
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AngeliqDrospirenone (0.5 mg/1) + Estradiol (1 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2010-09-29Not applicableUs
AngeliqDrospirenone (1.0 mg) + Estradiol (1.0 mg)TabletOralBayer2008-10-20Not applicableCanada
AngeliqDrospirenone (0.5 mg/1) + Estradiol (1 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2005-11-28Not applicableUs
AngeliqDrospirenone (0.25 mg/1) + Estradiol (0.5 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2012-02-29Not applicableUs
BeyazDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) + Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1)KitBayer2010-10-07Not applicableUs50419 40720180113 27003 xgvnkl
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitRpk Pharmaceuticals, Inc.2015-08-17Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitJubilant Cadista Pharmaceuticals Inc2018-11-30Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)KitNivagen Pharmaceuticals, Inc.2017-11-01Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)KitLupin Pharmaceuticals2012-12-31Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)KitLupin Pharmaceuticals2012-12-31Not applicableUs
Categories
UNII
N295J34A25
CAS number
67392-87-4
Weight
Average: 366.4932
Monoisotopic: 366.219494826
Chemical Formula
C24H30O3
InChI Key
METQSPRSQINEEU-HXCATZOESA-N
InChI
InChI=1S/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1
IUPAC Name
(1R,2R,4R,10R,11S,14S,15S,16S,18S,19S)-10,14-dimethylspiro[hexacyclo[9.8.0.0²,⁴.0⁵,¹⁰.0¹⁴,¹⁹.0¹⁶,¹⁸]nonadecane-15,2'-oxolan]-5-ene-5',7-dione
SMILES
[H][C@@]12C[C@]1([H])[C@@]1([H])[C@]3([H])[C@]4([H])C[C@]4([H])[C@@]4(CCC(=O)O4)[C@@]3(C)CC[C@]1([H])[C@@]1(C)CCC(=O)C=C21

Pharmacology

Indication

For the prevention of pregnancy in women who elect an oral contraceptive.

Associated Conditions
Associated Therapies
Pharmacodynamics

Drospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone. As such it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic.

Mechanism of action

Progestins such as drospirenone 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.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
AMineralocorticoid receptor
antagonist
Human
AAndrogen receptor
antagonist
Human
Absorption

Oral bioavailability is approximately 76%.

Volume of distribution
Not Available
Protein binding

95-97%

Metabolism

Extensively metabolized following oral or intravenous administration. The two major metabolites are inactive and are formed independent of the CYP450 enzyme system. The metabolites are the acid form of drospirenone formed by opening of the lactone ring and the 4,5-dihydro-drospirenone-3-sulfate.

Route of elimination
Not Available
Half life

30 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinDrospirenone may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinDrospirenone may decrease the anticoagulant activities of (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may increase the hyperkalemic activities of Drospirenone.
1,10-Phenanthroline1,10-Phenanthroline may increase the neuromuscular blocking activities of Drospirenone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Drospirenone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Drospirenone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Drospirenone.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Drospirenone.
6-Deoxyerythronolide BThe metabolism of Drospirenone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Drospirenone.
Food Interactions
  • Food reduces the rate of absorption, but not the extent of absorption.

References

Synthesis Reference

DOI: 10.1002/cjoc.201201147

General References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Wichianpitaya J, Taneepanichskul S: A comparative efficacy of low-dose combined oral contraceptives containing desogestrel and drospirenone in premenstrual symptoms. Obstet Gynecol Int. 2013;2013:487143. doi: 10.1155/2013/487143. Epub 2013 Feb 20. [PubMed:23577032]
External Links
Human Metabolome Database
HMDB0015467
KEGG Drug
D03917
PubChem Compound
68873
PubChem Substance
46507653
ChemSpider
62105
ChEBI
50838
ChEMBL
CHEMBL1509
Therapeutic Targets Database
DAP001206
PharmGKB
PA164749409
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Drospirenone
ATC Codes
G03FA17 — Drospirenone and estrogenG03AC10 — DrospirenoneG03AA12 — Drospirenone and ethinylestradiol
FDA label
Download (292 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingSupportive CareEndometriosis of Uterus1
1CompletedNot AvailableHealthy Volunteers2
1CompletedOtherContraception1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentContraception2
1RecruitingOtherHealthy Volunteers1
1RecruitingPreventionContraception1
1TerminatedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedTreatmentHealthy Volunteers1
1Unknown StatusTreatmentPolycystic Ovaries Syndrome1
1, 2CompletedPreventionContraception / Hemostasis Parameter / Liver Metabolism1
2CompletedPreventionContraception1
2CompletedPreventionPrevention of Pregnancy1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / One to five years postmenopausal / Pre-Hypertension1
2CompletedTreatmentOral Contraceptives (OC)1
2TerminatedTreatmentDepression / PMDD / Premenstrual Dysphoric Disorder / Premenstrual Syndrome1
2TerminatedTreatmentHidradenitis Suppurativa (HS)1
3Active Not RecruitingPreventionContraception1
3Active Not RecruitingTreatmentContraception1
3CompletedPreventionContraception9
3CompletedPreventionContraception / Neural Tube Defects (NTDs) / Oral Contraceptives (OC)1
3CompletedPreventionContraception / Oral Contraceptives (OC) / Ovulation Inhibition1
3CompletedTreatmentAcne Vulgaris4
3CompletedTreatmentContraception1
3CompletedTreatmentDysmenorrhea1
3CompletedTreatmentEndometriosis1
3CompletedTreatmentHealthy Volunteers1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / One to five years postmenopausal1
3CompletedTreatmentOral Contraceptives (OC)1
3CompletedTreatmentPolycystic Ovaries Syndrome2
3CompletedTreatmentPremenstrual Dysphoric Disorder ( PMDD)1
3CompletedTreatmentPremenstrual Syndrome1
3CompletedTreatmentPrimary Dysmenorrhoea1
3CompletedTreatmentVasomotor Symptoms2
3Unknown StatusNot AvailableContraceptive Affecting Blood Pressure / Contraceptive Affecting the Autonomic Nervous System1
3WithdrawnNot AvailableMetrorrhagia1
3WithdrawnTreatmentContraception1
3WithdrawnTreatmentDysmenorrhea1
4CompletedNot AvailableBlood Pressures / Contraception1
4CompletedNot AvailableContraception2
4CompletedBasic ScienceAdverse Effect of Oral Contraceptives, Subsequent Encounter1
4CompletedPreventionCardiovascular Disease (CVD)1
4CompletedTreatmentContraception1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentPolycystic Ovaries Syndrome2
4CompletedTreatmentPremenstrual Dysphoric Disorder1
4CompletedTreatmentPremenstrual Syndrome1
4CompletedTreatmentPrimary Dysmenorrhoea1
4CompletedTreatmentOne to five years postmenopausal1
4Enrolling by InvitationTreatmentBody Weight Changes1
4Unknown StatusNot AvailableDysmenorrhea / Endometriotic Cysts / Painful Intercourse / Pelvic Pain1
4Unknown StatusPreventionHyperandrogenism / Menstrual Irregularities / Polycystic Ovarian Syndrome1
4Unknown StatusTreatmentContraceptive Methods Comparison1
Not AvailableActive Not RecruitingNot AvailableDysmenorrhea1
Not AvailableCompletedNot AvailableAcne / Contraception / Premenstrual Syndrome1
Not AvailableCompletedNot AvailableContraception4
Not AvailableCompletedNot AvailableMetabolic Syndromes / Polycystic Ovaries Syndrome1
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO) / Postmenopausal Period1
Not AvailableCompletedTreatmentDepression / Premenstrual Syndrome1
Not AvailableCompletedTreatmentEstro-progestin Drugs / Polycystic Ovaries Syndrome1
Not AvailableCompletedTreatmentOne to five years postmenopausal1
Not AvailableNot Yet RecruitingTreatmentPremature Menopause / Primary Ovarian Insufficiency1
Not AvailableRecruitingNot AvailableInfertilities1
Not AvailableUnknown StatusTreatmentEndothelial Dysfunction / Polycystic Ovaries Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral
KitOral
TabletOral
Kit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6787531No2004-09-072020-08-31Us
US6933395No2005-08-232017-08-11Us
US8906890No2014-12-092031-10-22Us
US6987101No2006-01-172017-12-22Us
US7163931No2007-01-162021-12-20Us
US6958326No2005-10-252021-12-20Us
US5798338No1998-08-252015-07-10Us
US6441168No2002-08-272022-07-30Us
US8617597No2013-12-312030-02-08Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00225 mg/mLALOGPS
logP2.36ALOGPS
logP3.37ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.68 m3·mol-1ChemAxon
Polarizability41.81 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6376
P-glycoprotein substrateSubstrate0.6524
P-glycoprotein inhibitor IInhibitor0.6171
P-glycoprotein inhibitor IINon-inhibitor0.6726
Renal organic cation transporterNon-inhibitor0.7005
CYP450 2C9 substrateNon-substrate0.796
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6964
CYP450 1A2 substrateNon-inhibitor0.5534
CYP450 2C9 inhibitorNon-inhibitor0.8665
CYP450 2D6 inhibitorNon-inhibitor0.9336
CYP450 2C19 inhibitorNon-inhibitor0.7754
CYP450 3A4 inhibitorNon-inhibitor0.8355
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8541
Ames testNon AMES toxic0.9163
CarcinogenicityNon-carcinogens0.9505
BiodegradationNot ready biodegradable0.9757
Rat acute toxicity1.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9393
hERG inhibition (predictor II)Non-inhibitor0.8215
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (37.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as spironolactones and derivatives. These are steroid lactones with a structure based on the spironolactone skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Spironolactones and derivatives
Alternative Parents
Cyclohexenones / Gamma butyrolactones / Tetrahydrofurans / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Spironolactone / Cyclohexenone / Gamma butyrolactone / Tetrahydrofuran / Cyclic ketone / Lactone / Ketone / Carboxylic acid ester / Oxacycle / Organoheterocyclic compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
3-oxo steroid, 3-oxo Delta(4)-steroid, steroid lactone (CHEBI:50838)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Bray JD, Jelinsky S, Ghatge R, Bray JA, Tunkey C, Saraf K, Jacobsen BM, Richer JK, Brown EL, Winneker RC, Horwitz KB, Lyttle CR: Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells. J Steroid Biochem Mol Biol. 2005 Dec;97(4):328-41. Epub 2005 Sep 12. [PubMed:16157482]
  3. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [PubMed:8922878]
  4. Arias-Loza PA, Hu K, Schafer A, Bauersachs J, Quaschning T, Galle J, Jazbutyte V, Neyses L, Ertl G, Fritzemeier KH, Hegele-Hartung C, Pelzer T: Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats. Hypertension. 2006 Nov;48(5):994-1001. Epub 2006 Sep 25. [PubMed:17000933]
  5. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. [PubMed:16291771]
  6. Sitruk-Ware R: New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drugs Aging. 2004;21(13):865-83. [PubMed:15493951]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [PubMed:8922878]
  3. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. [PubMed:7625729]
  4. Oelkers WK: Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996 Apr;61(4):166-71. [PubMed:8732994]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Maia H Jr, Casoy J, Athayde C, Valente Filho J, Coutinho EM: The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium. Eur J Contracept Reprod Health Care. 2010 Feb;15(1):35-40. doi: 10.3109/13625180903383928. [PubMed:20063991]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Koitka M, Hochel J, Gieschen H, Borchert HH: Improving the ex vivo stability of drug ester compounds in rat and dog serum: inhibition of the specific esterases and implications on their identity. J Pharm Biomed Anal. 2010 Feb 5;51(3):664-78. doi: 10.1016/j.jpba.2009.09.023. Epub 2009 Sep 23. [PubMed:19850433]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wiesinger H, Berse M, Klein S, Gschwend S, Hochel J, Zollmann FS, Schutt B: Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. Br J Clin Pharmacol. 2015 Dec;80(6):1399-410. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. [PubMed:26271371]

Drug created on July 08, 2007 11:03 / Updated on December 14, 2018 17:09