Details of the Drug

General Information of Drug (ID: DMZK0FQ)

Drug Name
Oestradiol valerate and dienogest
Synonyms
Dienogest; 65928-58-7; Dienogestrel; Dienogestum; Dienogestril; Dinagest; Natazia; Endometrion; Visanne; STS-557; STS 557; Dienogestum [Latin]; UNII-46M3EV8HHE; MJR-35; 17alpha-17-Hydroxy-3-oxo-19-norpregna-4,9-diene-21-nitrile; BAY86-5258; BAY 86-5258; 46M3EV8HHE; CHEBI:70708; 17-alpha-Cyanomethyl-17-beta-hydroxy-estra-4,9(10)-dien-3-one; 2-[(8S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl]acetonitrile; 17-alpha-Cyanomethyl-17-beta-hydroxyestra-4,9(10)-diene-3-one; Natazia (TN)
Indication
Disease Entry ICD 11 Status REF
Contraception QA21 Approved [1]
Endometriosis GA10 Approved [2], [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 311.4
Topological Polar Surface Area (xlogp) 1.8
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Bioavailability
The bioavailability of drug is 0.63% [3]
Clearance
The clearance of drug is 64 mL/min [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 9 - 10 hours [4]
Metabolism
The drug is metabolized via the CYP3A4 [3]
Unbound Fraction
The unbound fraction of drug in plasma is 0.1% [5]
Vd
The volume of distribution (Vd) of drug is 40 L [4]
Chemical Identifiers
Formula
C20H25NO2
IUPAC Name
2-[(8S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl]acetonitrile
Canonical SMILES
C[C@]12CCC3=C4CCC(=O)C=C4CC[C@H]3[C@@H]1CC[C@]2(CC#N)O
InChI
InChI=1S/C20H25NO2/c1-19-8-6-16-15-5-3-14(22)12-13(15)2-4-17(16)18(19)7-9-20(19,23)10-11-21/h12,17-18,23H,2-10H2,1H3/t17-,18+,19+,20-/m1/s1
InChIKey
AZFLJNIPTRTECV-FUMNGEBKSA-N
Cross-matching ID
PubChem CID
68861
ChEBI ID
CHEBI:70708
CAS Number
65928-58-7
DrugBank ID
DB09123
TTD ID
D04CBI
INTEDE ID
DR0490

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Oestradiol valerate and dienogest (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Emapalumab DMZG5WL Moderate Altered metabolism of Oestradiol valerate and dienogest due to Emapalumab alters the formation of CYP450 enzymes. Adaptive immunity immunodeficiency [4A01] [16]
Ag-221 DMS0ZBI Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Ag-221 mediated induction of CYP450 enzyme. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [17]
Pexidartinib DMS2J0Z Major Increased metabolism of Oestradiol valerate and dienogest caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [18]
Eslicarbazepine DMZREFQ Major Increased metabolism of Oestradiol valerate and dienogest caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [19]
Lesinurad DMUR64T Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [17]
Brigatinib DM7W94S Major Increased metabolism of Oestradiol valerate and dienogest caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [20]
Calaspargase pegol DMQZBXI Moderate Decreased metabolism of Oestradiol valerate and dienogest caused by Calaspargase pegol mediated hepatotoxicity. Malignant haematopoietic neoplasm [2B33] [21]
LGX818 DMNQXV8 Major Increased metabolism of Oestradiol valerate and dienogest caused by LGX818 mediated induction of CYP450 enzyme. Melanoma [2C30] [20]
Ixekizumab DMXW92T Moderate Altered metabolism of Oestradiol valerate and dienogest due to Ixekizumab alters the formation of CYP450 enzymes. Psoriasis [EA90] [16]
Sarilumab DMOGNXY Moderate Altered metabolism of Oestradiol valerate and dienogest due to Sarilumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [16]
Pitolisant DM8RFNJ Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Pitolisant mediated induction of CYP450 enzyme. Somnolence [MG42] [22]
⏷ Show the Full List of 11 DDI Information of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 7654).
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Bayer Inc: VISANNE (2mg dienogest tablets) Product Monograph
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Progestogens in menopausal hormone therapy. Prz Menopauzalny. 2015 Jun;14(2):134-43.
7 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
8 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
9 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
10 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
12 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
13 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
15 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
16 Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
17 Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
18 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
19 Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32. [PMID: 3408633]
20 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
21 Cerner Multum, Inc. "Australian Product Information.".
22 Cerner Multum, Inc. "UK Summary of Product Characteristics.".