Details of the Drug

General Information of Drug (ID: DMDGCQP)

Drug Name
Norethindrone acetate
Synonyms
Noresthisterone; Norethadrone; Norethisteron; Norethisterone; Norethisteronum; Norethyndron; Norethynodron; Norethynodrone; Noretisterona; Norfor; Norgestin; Noriday; Norluten; Norlutin; Norluton; Norpregneninlone; Norpregneninolone; Primolut-N; Proluteasi; Synphase; Triella; Utovlan; Utovlar; norethindrone; 19-Nor-ethindrone; 19-Norethisterone; 68-22-4; Anovulatorio; Anovule; Camila; Ciclovulan; Conludaf; Conludag; Ethinylnortestosterone; Gestest; Microneth; Micronett; Micronor; Micronovum; Mini-Pe; Mini-pill; Minovlar; Nor-QD; Noralutin; Norcolut; 1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 340.5
Logarithm of the Partition Coefficient (xlogp) 3.5
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 30 to 37 mcgh/L [1]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 5.39 to 7.36 mcg/L [1]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1-2 h [1]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Bioavailability
The bioavailability of drug is 64% [1]
Clearance
The clearance of drug is 0.4 L/h/kg [3]
Elimination
More than 50% of the administered dose was eliminated in the urine and 20-40% was eliminated in the feces [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 8 - 10 hours [5]
Metabolism
The drug is metabolized via the liver [6]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.62939 micromolar/kg/day [7]
Vd
The volume of distribution (Vd) of drug is 4 L/kg [8]
Water Solubility
The ability of drug to dissolve in water is measured as 0.005 mg/mL [2]
Chemical Identifiers
Formula
C22H28O3
IUPAC Name
[(8R,9S,10R,13S,14S,17R)-17-ethynyl-13-methyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate
Canonical SMILES
CC(=O)OC1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34)C)C#C
InChI
IMONTRJLAWHYGT-ZCPXKWAGSA-N
InChIKey
1S/C22H28O3/c1-4-22(25-14(2)23)12-10-20-19-7-5-15-13-16(24)6-8-17(15)18(19)9-11-21(20,22)3/h1,13,17-20H,5-12H2,2-3H3/t17-,18+,19+,20-,21-,22-/m0/s1
Cross-matching ID
PubChem CID
5832
ChEBI ID
CHEBI:7628
CAS Number
51-98-9
INTEDE ID
DR1750

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 [9]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [10]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [11]
Beta-HSD adrenal and gonadal type (HSD3B2) DEN0GVQ 3BHS2_HUMAN Substrate [12]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [11]
Aldo-keto reductase 1C4 (AKR1C4) DEAJN47 AK1C4_HUMAN Substrate [12]
Aldo-keto reductase 1D1 (AKR1D1) DEVON3M AK1D1_HUMAN Substrate [12]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Gene/Protein Processing [13]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Protein Interaction/Cellular Processes [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 FDA Approved Drug Products: Lo Loestrin Fe oral tablets
2 BDDCS applied to over 900 drugs
3 Kuhnz W, Gieschen H: Predicting the oral bioavailability of 19-nortestosterone progestins in vivo from their metabolic stability in human liver microsomal preparations in vitro. Drug Metab Dispos. 1998 Nov;26(11):1120-7.
4 Hammer HF, Hammer J, Gasche C: [Polyethylene glycol (Macrogol)--an overview of its use in diagnosis and therapy of gastrointestinal diseases]. Wien Klin Wochenschr. 2000 Jan 28;112(2):53-60.
5 Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis. Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):399-415. doi: 10.1080/17425255.2018.1461840. Epub 2018 Apr 10.
6 Chen Z, Stamler JS: Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med. 2006 Nov;16(8):259-65. doi: 10.1016/j.tcm.2006.05.001.
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 Sahlberg BL: The characterization of sulphated metabolites of norethindrone in human milk after oral administration of contraceptive steroids. J Steroid Biochem. 1987 Apr;26(4):481-5. doi: 10.1016/0022-4731(87)90060-4.
9 Identification of the human cytochrome P450 enzymes involved in the in vitro biotransformation of lynestrenol and norethindrone. J Steroid Biochem Mol Biol. 2008 May;110(1-2):56-66.
10 Drug Interactions Flockhart Table
11 The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther. 2003 Dec;74(6):525-35.
12 Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):213-22.
13 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
14 Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat. Mol Cell Endocrinol. 2010 Oct 26;328(1-2):16-21. doi: 10.1016/j.mce.2010.06.010. Epub 2010 Jun 25.