Details of the Drug

General Information of Drug (ID: DM27U4Y)

Drug Name
Desogestrel
Synonyms
Cerazette; Desogen; Desogestrelum; Organon Brand of Desogestrel; ORG 2969; Desogestrelum [INN-Latin]; Desogestrel (USAN/INN); Desogestrel [USAN:BAN:INN]; Alpha-pregn-4-en-20-yn-17-ol, 13-Ethyl-11-methylene-18,19-dinor-17; (17alpha)-13-Ethyl-11-methylene-18,19-dinorpregn-4-en-20-yn-17-ol; (8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol; 13 Ethyl 11 methylene 18,19 dinor 17 alpha pregn 4 en 20 yn 17 ol; 13-Ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol; 13-Ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol; 17alpha-ethynyl-11-methylidene-18a-homo-estr-4-en-17beta-ol
Indication
Disease Entry ICD 11 Status REF
Contraception QA21 Approved [1], [2]
Therapeutic Class
Contraceptive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 310.5
Topological Polar Surface Area (xlogp) 4.9
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 1
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 2000 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 48 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.5 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Bioavailability
The bioavailability of drug is 39% [3]
Clearance
The clearance of drug is 2 mL/min/kg [5]
Elimination
The elimination of desogestrel is only done as the metabolites and not as the unchanged drug and about 85% of the administered dose can be excreted as metabolites after 6-8 days [5]
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 first-pass hepatic metabolism to form the major biologically active metabolite of desogestrel [6]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00805 micromolar/kg/day [7]
Vd
The volume of distribution (Vd) of drug is 1.5 L/kg [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.32 mg/mL [4]
Chemical Identifiers
Formula
C22H30O
IUPAC Name
(8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol
Canonical SMILES
CC[C@]12CC(=C)[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CCCC[C@H]34
InChI
InChI=1S/C22H30O/c1-4-21-14-15(3)20-17-9-7-6-8-16(17)10-11-18(20)19(21)12-13-22(21,23)5-2/h2,8,17-20,23H,3-4,6-7,9-14H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1
InChIKey
RPLCPCMSCLEKRS-BPIQYHPVSA-N
Cross-matching ID
PubChem CID
40973
ChEBI ID
CHEBI:4453
CAS Number
54024-22-5
DrugBank ID
DB00304
TTD ID
D06CGB
INTEDE ID
DR0438

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Progesterone receptor (PGR) TTUV8G9 PRGR_HUMAN Modulator [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Contraception
ICD Disease Classification QA21
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Progesterone receptor (PGR) DTT PGR 3.26E-38 -3.79 -2.5
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 1.07E-03 -2.00E-01 -3.54E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 4.46E-05 -2.53E-01 -2.36E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 2.20E-02 -1.08E-01 -2.31E-01
Molecular Expression Atlas (MEA) 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 Desogestrel (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Metreleptin DM1NOEK Moderate Decreased metabolism of Desogestrel caused by Metreleptin mediated inhibition of CYP450 enzyme. Acute diabete complication [5A2Y] [43]
Siltuximab DMGEATB Moderate Altered metabolism of Desogestrel due to Siltuximab alters the formation of CYP450 enzymes. Anemia [3A00-3A9Z] [44]
Clobazam - Lundbeck DMW1OQ0 Moderate Increased metabolism of Desogestrel caused by Clobazam - Lundbeck mediated induction of CYP450 enzyme. Anxiety disorder [6B00-6B0Z] [45]
Voriconazole DMAOL2S Moderate Decreased metabolism of Desogestrel caused by Voriconazole mediated inhibition of CYP450 enzyme. Aspergillosis [1F20] [46]
Posaconazole DMUL5EW Moderate Decreased metabolism of Desogestrel caused by Posaconazole mediated inhibition of CYP450 enzyme. Aspergillosis [1F20] [46]
Telithromycin DMZ4P3A Moderate Decreased metabolism of Desogestrel caused by Telithromycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [47]
Lapatinib DM3BH1Y Moderate Decreased metabolism of Desogestrel caused by Lapatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [48]
Atorvastatin DMF28YC Minor Decreased metabolism of Desogestrel caused by Atorvastatin mediated inhibition of CYP450 enzyme. Cardiovascular disease [BA00-BE2Z] [49]
Ivacaftor DMZC1HS Moderate Decreased metabolism of Desogestrel caused by Ivacaftor mediated inhibition of CYP450 enzyme. Cystic fibrosis [CA25] [50]
MK-8228 DMOB58Q Moderate Decreased metabolism of Desogestrel caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [51]
Aprepitant DM053KT Moderate Increased metabolism of Desogestrel caused by Aprepitant mediated induction of CYP450 enzyme. Depression [6A70-6A7Z] [45]
Nefazodone DM4ZS8M Moderate Decreased metabolism of Desogestrel caused by Nefazodone mediated inhibition of CYP450 enzyme. Depression [6A70-6A7Z] [48]
Oxcarbazepine DM5PU6O Major Increased metabolism of Desogestrel caused by Oxcarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [52]
Rufinamide DMWE60C Moderate Increased metabolism of Desogestrel caused by Rufinamide mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [53]
Telaprevir DMMRV29 Major Increased metabolism of Desogestrel caused by Telaprevir mediated induction of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [45]
Rifapentine DMCHV4I Major Increased metabolism of Desogestrel caused by Rifapentine mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [54]
Efavirenz DMC0GSJ Moderate Increased metabolism of Desogestrel caused by Efavirenz mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [45]
Saquinavir DMG814N Moderate Decreased metabolism of Desogestrel caused by Saquinavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [51]
Darunavir DMN3GCH Moderate Decreased metabolism of Desogestrel caused by Darunavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [55]
BMS-201038 DMQTAGO Moderate Decreased metabolism of Desogestrel caused by BMS-201038 mediated inhibition of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [56]
Miltefosine DMND304 Moderate Altered absorption of Desogestrel caused by Miltefosine. Leishmaniasis [1F54] [43]
Glycerol phenylbutyrate DMDGRQO Moderate Increased metabolism of Desogestrel caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme. Liver disease [DB90-DB9Z] [53]
Vemurafenib DM62UG5 Moderate Increased metabolism of Desogestrel caused by Vemurafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [57]
Dabrafenib DMX6OE3 Major Increased metabolism of Desogestrel caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [45]
Exjade DMHPRWG Moderate Increased metabolism of Desogestrel caused by Exjade mediated induction of CYP450 enzyme. Mineral absorption/transport disorder [5C64] [56]
Bexarotene DMOBIKY Major Increased metabolism of Desogestrel caused by Bexarotene mediated induction of CYP450 enzyme. Mycosis fungoides [2B01] [45]
E-2007 DMJDYNQ Moderate Increased metabolism of Desogestrel caused by E-2007 mediated induction of CYP450 enzyme. Neuropathy [8C0Z] [53]
Tocilizumab DM7J6OR Moderate Altered metabolism of Desogestrel due to Tocilizumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [44]
Rilonacept DMGLUQS Moderate Altered metabolism of Desogestrel due to Rilonacept alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [44]
Sarilumab DMOGNXY Moderate Altered metabolism of Desogestrel due to Sarilumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [44]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Desogestrel caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [43]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Desogestrel caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [53]
Pitolisant DM8RFNJ Moderate Increased metabolism of Desogestrel caused by Pitolisant mediated induction of CYP450 enzyme. Somnolence [MG42] [53]
Tizanidine DMR2IQ4 Major Decreased metabolism of Desogestrel caused by Tizanidine mediated inhibition of CYP450 enzyme. Tonus and reflex abnormality [MB47] [58]
⏷ Show the Full List of 34 DDI Information of This Drug

References

1 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: 7065).
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses. Drug Test Anal. 2018 Mar 25. doi: 10.1002/dta.2378.
4 BDDCS applied to over 900 drugs
5 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6 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.
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 Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
9 The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel. Br J Clin Pharmacol. 2005 Jul;60(1):69-75.
10 The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel. J Pharmacol Exp Ther. 1998 Dec;287(3):975-82.
11 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.
12 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
13 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.
14 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
15 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.
16 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.
17 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
18 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.
19 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.
20 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
21 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
22 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
23 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
24 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
25 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
26 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
27 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
28 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
29 High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
30 Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
31 CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
32 Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
33 Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
34 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
35 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
36 Clinical pipeline report, company report or official report of lipocine.
37 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
38 Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
39 Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
40 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
41 Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
42 Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84.
43 Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
44 Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
45 Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception.".
46 Lazar JD, Wilner KD "Drug interactions with fluconazole." Rev Infect Dis 12 Suppl 3 (1990): s327-33. [PMID: 2330488]
47 Product Information. Ketek (telithromycin). Aventis Pharmaceuticals, Bridgewater, NJ.
48 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
49 Product Information. Lipitor (atorvastatin). Parke-Davis, Morris Plains, NJ.
50 Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83. [PMID: 9834039]
51 Cerner Multum, Inc. "Australian Product Information.".
52 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]
53 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
54 Back DJ, Breckenridge AM, Crawford F, et al. "The effect of rifampicin on norethisterone pharmacokinetics." Eur J Clin Pharmacol 15 (1979): 193-7. [PMID: 37091]
55 Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
56 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
57 Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61. [PMID: 7009137]
58 Granfors MT, Backman JT, Laitila J, Neuvonen PJ "Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2." Clin Pharmacol Ther 78 (2005): 400-11. [PMID: 16198659]