Details of the Drug

General Information of Drug (ID: DM1A9W3)

Drug Name

Drospirenone

Synonyms

DRSP; Dehydrospirorenone; Dihydrospirorenone; Drospirenona; Drospirenonum; Drospirenone [INN]; ZK 30595; ZK30595; Angeliq, Drospirenone; Drospirenona [INN-Spanish]; Drospirenonum [INN-Latin]; SH-470; ZK-30595; Drospirenone (JAN/USAN/INN); (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3',4',6,6a,7,8,9,10,11,12,13,14,15,15a,16-Hexadecahydro-10,13-dimethylspiro-(17H-dicyclopropa(6,7:15,16)cyclopenta(a)phenanthrene-17,2'(5'H)-furan)-3,5'(2H)-dione; 1,2-Dihydrospirorenone; 1,2-dihydro-spirorenone; 17-Hydroxy-6beta,7beta:15beta,16beta-dimethylene-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid, gamma-lactone; 3-oxo-6alpha,7alpha,15alpha,16alpha-tetrahydro-7'H,16'H-dicyclopropa[6,7;15,16]-17alpha-pregn-4-ene-21,17-carbolactone; 6-beta,7-beta;15-beta,16-beta-Dimethylene-3-oxo-17-alpha-pregn-4-ene-21,17-carbolactone; 6beta,7beta,15beta,16beta-dimethylen-3-oxo-17alpha-pregn-4-en-21,17-carbolacton; 6beta,7beta,15beta,16beta-dimethylene-3-oxo-17alpha-pregn-4-ene-21,17 carbolactone; 6beta,7beta;15beta,16beta-Dimethylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone; Spiro(17H-dicyclopropa(6,7:15,16)cyclopenta(a)phenanthrene-17,2'(5'H)-furan)-3,5'(2H)-dione, 1,3',4',6,7,8,9,10,11,12,13,14,15,16,20,21-hexadecahydro-10,13-dimethyl-, (6R-(6alpha,7alpha,8beta,9alpha,10beta,13beta,14alpha,15alpha,16alpha,17beta

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1]
Contraception	QA21	Approved	[2]
Hot flushes	GA30	Approved	[1]
Obsolete atrophic vulva	N.A.	Approved	[1]
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Therapeutic Class

Contraceptive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

366.5

Logarithm of the Partition Coefficient (xlogp)

3.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 60-87 mcg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-2 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Bioavailability: The bioavailability of drug is 76% [3]
Clearance: The clearance of drug is 1.2-1.5 mL/min/kg [5]
Elimination: Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 30 hours [6]
Metabolism: The drug is metabolized via the opening of its lactone ring [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.117 micromolar/kg/day [7]
Vd: The volume of distribution (Vd) of drug is 4 L/kg [8]

Chemical Identifiers

Formula: C24H30O3
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]nonadec-5-ene-15,5'-oxolane]-2',7-dione
Canonical SMILES: C[C@]12CCC(=O)C=C1[C@@H]3C[C@@H]3[C@@H]4[C@@H]2CC[C@]5([C@H]4[C@@H]6C[C@@H]6[C@@]57CCC(=O)O7)C
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
InChIKey: METQSPRSQINEEU-HXCATZOESA-N

Cross-matching ID

PubChem CID: 68873
ChEBI ID: CHEBI:50838
CAS Number: 67392-87-4
DrugBank ID: DB01395
TTD ID: D0Z4ZT
VARIDT ID: DR00825
INTEDE ID: DR0551

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mineralocorticoid receptor (MR)	TT26PHO	MCR_HUMAN	Binder	[9]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Protein Interaction/Cellular Processes	[11]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[12]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Protein Interaction/Cellular Processes	[13]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Acne vulgaris

ICD Disease Classification

ED80

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Mineralocorticoid receptor (MR)	DTT	NR3C2	7.31E-01	-5.31E-04	-1.53E-03
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Drospirenone (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Metreleptin	DM1NOEK	Moderate	Decreased metabolism of Drospirenone caused by Metreleptin mediated inhibition of CYP450 enzyme.	Acute diabete complication [5A2Y]	[14]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Drospirenone caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[15]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Drospirenone caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[16]
Emapalumab	DMZG5WL	Moderate	Altered metabolism of Drospirenone due to Emapalumab alters the formation of CYP450 enzymes.	Adaptive immunity immunodeficiency [4A01]	[17]
Siltuximab	DMGEATB	Moderate	Altered metabolism of Drospirenone due to Siltuximab alters the formation of CYP450 enzymes.	Anemia [3A00-3A9Z]	[17]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Drospirenone caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[18]
Ag-221	DMS0ZBI	Moderate	Decreased metabolism of Drospirenone caused by Ag-221 mediated inhibition of CYP450 enzyme.	BCR-ABL1-negative chronic myeloid leukaemia [2A41]	[19]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Drospirenone caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[20]
Tucatinib	DMBESUA	Major	Decreased metabolism of Drospirenone caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[18]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Drospirenone caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[17]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Drospirenone caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[18]
Cenobamate	DM8KLU9	Moderate	Increased metabolism of Drospirenone caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Drospirenone caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[21]
Brivaracetam	DMSEPK8	Minor	Increased metabolism of Drospirenone caused by Brivaracetam mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Drospirenone caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[18]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of Drospirenone caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Drospirenone caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[22]
Boceprevir	DMBSHMF	Major	Decreased metabolism of Drospirenone caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[18]
Telaprevir	DMMRV29	Major	Decreased metabolism of Drospirenone caused by Telaprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[18]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Drospirenone caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[18]
BMS-201038	DMQTAGO	Moderate	Decreased metabolism of Drospirenone caused by BMS-201038 mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[23]
TAK-491	DMCF6SX	Moderate	Increased risk of hyperkalemia by the combination of Drospirenone and TAK-491.	Hypertension [BA00-BA04]	[24]
Tolvaptan	DMIWFRL	Moderate	Increased risk of hyperkalemia by the combination of Drospirenone and Tolvaptan.	Hypo-osmolality/hyponatraemia [5C72]	[25]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Drospirenone caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[26]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Drospirenone caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[27]
Miltefosine	DMND304	Moderate	Altered absorption of Drospirenone caused by Miltefosine.	Leishmaniasis [1F54]	[28]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Increased metabolism of Drospirenone caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[17]
Brigatinib	DM7W94S	Major	Increased metabolism of Drospirenone caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[29]
Ceritinib	DMB920Z	Major	Decreased metabolism of Drospirenone caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[18]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Drospirenone caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[16]
Artemether	DM48QOT	Moderate	Increased metabolism of Drospirenone caused by Artemether mediated induction of CYP450 enzyme.	Malaria [1F40-1F45]	[30]
Idelalisib	DM602WT	Major	Decreased metabolism of Drospirenone caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[18]
Vemurafenib	DM62UG5	Moderate	Increased metabolism of Drospirenone caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[16]
LGX818	DMNQXV8	Major	Increased metabolism of Drospirenone caused by LGX818 mediated induction of CYP450 enzyme.	Melanoma [2C30]	[31]
Dabrafenib	DMX6OE3	Major	Increased metabolism of Drospirenone caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[32]
Exjade	DMHPRWG	Moderate	Increased metabolism of Drospirenone caused by Exjade mediated induction of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[33]
Carfilzomib	DM48K0X	Major	Additive thrombogenic effects by the combination of Drospirenone and Carfilzomib.	Multiple myeloma [2A83]	[17]
E-2007	DMJDYNQ	Moderate	Increased metabolism of Drospirenone caused by E-2007 mediated induction of CYP450 enzyme.	Neuropathy [8C0Z]	[18]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Drospirenone caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[17]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Drospirenone caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[34]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Drospirenone caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[35]
Choline salicylate	DM8P137	Moderate	Increased risk of hyperkalemia by the combination of Drospirenone and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[24]
Lonafarnib	DMGM2Z6	Major	Decreased metabolism of Drospirenone caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[18]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Drospirenone caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[16]
Ustekinumab	DMHTYK3	Moderate	Altered metabolism of Drospirenone due to Ustekinumab alters the formation of CYP450 enzymes.	Psoriasis [EA90]	[17]
Ixekizumab	DMXW92T	Moderate	Altered metabolism of Drospirenone due to Ixekizumab alters the formation of CYP450 enzymes.	Psoriasis [EA90]	[17]
Salsalate	DM13P4C	Moderate	Increased risk of hyperkalemia by the combination of Drospirenone and Salsalate.	Rheumatoid arthritis [FA20]	[24]
Tocilizumab	DM7J6OR	Moderate	Altered metabolism of Drospirenone due to Tocilizumab alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[17]
Canakinumab	DM8HLO5	Moderate	Altered metabolism of Drospirenone due to Canakinumab alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[17]
Rilonacept	DMGLUQS	Moderate	Altered metabolism of Drospirenone due to Rilonacept alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[17]
Golimumab	DMHZV7X	Moderate	Altered metabolism of Drospirenone due to Golimumab alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[17]
Sarilumab	DMOGNXY	Moderate	Altered metabolism of Drospirenone due to Sarilumab alters the formation of CYP450 enzymes.	Rheumatoid arthritis [FA20]	[17]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Drospirenone caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[18]
Armodafinil	DMGB035	Moderate	Increased metabolism of Drospirenone caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[18]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Drospirenone caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[17]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Drospirenone caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[36]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Drospirenone caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[16]
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References

1	Drospirenone FDA Label
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2874).
3	Di L: Strategic approaches to optimizing peptide ADME properties. AAPS J. 2015 Jan;17(1):134-43. doi: 10.1208/s12248-014-9687-3. Epub 2014 Nov 4.
4	BDDCS applied to over 900 drugs
5	Breech LL, Braverman PK: Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder. Int J Womens Health. 2010 Aug 9;1:85-95.
6	Drospirenone: a novel progestin. Expert Opin Pharmacother. 2007 May;8(7):989-99. doi: 10.1517/14656566.8.7.989 .
7	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8	YAZ fda label
9	Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78.
10	Role of CYP3A in oral contraceptives clearance. Clin Transl Sci. 2018 May;11(3):251-260.
11	Identifying environmental chemicals as agonists of the androgen receptor by using a quantitative high-throughput screening platform. Toxicology. 2017 Jun 15;385:48-58. doi: 10.1016/j.tox.2017.05.001. Epub 2017 May 4.
12	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
13	Conception and pharmacodynamic profile of drospirenone. Steroids. 2003 Nov;68(10-13):891-905. doi: 10.1016/j.steroids.2003.08.008.
14	Product Information. Myalept (metreleptin). Bristol-Myers Squibb, Princeton, NJ.
15	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
16	Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35. [PMID: 2859674]
17	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18	Cerner Multum, Inc. "Australian Product Information.".
19	Product Information. Idhifa (enasidenib). Celgene Corporation, Summit, NJ.
20	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
21	EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
22	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
23	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
24	Product Information. Yasmin (drospirenone-ethinyl estradiol) Berlex Laboratories, Richmond, CA.
25	Product Information. Samsca (tolvaptan). Otsuka American Pharmaceuticals Inc, Rockville, MD.
26	Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
27	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
28	Product Information. Impavido (miltefosine). Paladin Therapeutics Inc, Wilmington, DE.
29	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
30	Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception.".
31	Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
32	Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception.".
33	Product Information. Desferal (deferoxamine). Novartis Pharmaceuticals, East Hanover, NJ.
34	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
35	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
36	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.