Details of the Drug

General Information of Drug (ID: DM8HDOL)

Drug Name
Phytonadione
Synonyms
Phyllochinon; Phyllohydroquinone; Phytomenadione; Fitomenadione [DCIT]; Phyllochinon [German]; LT00452032; Fitomenadiona [INN-Spanish]; Mephyton (TN); Phylloquinone (8CI); Phytomenadione (INN); Phytomenadionum [INN-Latin]; Phytonadione [USAN:JAN]; Vitamin K1 (TN); Vitamin K1 (VAN); Vitamin K1 (generic); Phythyl-menadion (GERMAN); Phytonadione (JP15/USP); 1,4-Naphthalenedione, 2-methyl-3-((2E,7R,11R)-3,7,11,15-tetramethyl-2-hexadecenyl)-, radical ion(1-); 2-(3,7,11,15-Tetramethylhexadec-2-enyl)-3-methylnaphthalene-1,4-dione; 2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalened-ione; 2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedione; 2-Methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)-1,4-naphthoquinone; 2-Methyl-3-phythyl-1,4-naphthochinon; 2-Methyl-3-phytyl-1,4-naphthochinon; 2-Methyl-3-phytyl-1,4-naphthochinon [German]; 2-methyl-3-(3,7,11,15-tetramethylhexadec-2-en-1-yl)naphthalene-1,4-dione; 2-methyl-3-[(E)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione; 3-Phytylmenadione
Indication
Disease Entry ICD 11 Status REF
Bleeding disorder GA20-GA21 Approved [1]
Osteoporosis FB83.0 Approved [2]
Vitamin K deficiency 5B59 Approved [1]
Autosomal dominant hypocalcemia 5A50.0Y Investigative [2]
Therapeutic Class
Vitamins
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 450.7
Logarithm of the Partition Coefficient (xlogp) 10.9
Rotatable Bond Count (rotbonds) 14
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4.7 +/- 0.8 h [3]
Clearance
The clearance of drug is 91 +/- 24 mL/min [4]
Elimination
Intravenous phylloquinone is 36% eliminated in the feces in 5 days and 22% recovered in urine in 3 days [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 22 minutes [5]
Metabolism
The drug is metabolized via the CYP4F2 [6]
Vd
The volume of distribution (Vd) of drug is 20 +/- 6 L [7]
Chemical Identifiers
Formula
C31H46O2
IUPAC Name
2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione
Canonical SMILES
CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
InChI
InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+/t23-,24-/m1/s1
InChIKey
MBWXNTAXLNYFJB-NKFFZRIASA-N
Cross-matching ID
PubChem CID
5284607
ChEBI ID
CHEBI:18067
CAS Number
79083-00-4
DrugBank ID
DB01022
TTD ID
D00FSV
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Vitamin K-dependent gamma-carboxylase (GGCX) TT76OLR VKGC_HUMAN Cofactor [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cytochrome P450 4F2 (CYP4F2) OTKILAER CP4F2_HUMAN Regulation of Drug Effects [9]
Matrix Gla protein (MGP) OTZWU3FU MGP_HUMAN Gene/Protein Processing [10]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Gene/Protein Processing [11]
Prothrombin (F2) OTNFSM49 THRB_HUMAN Gene/Protein Processing [12]
Vitamin K epoxide reductase complex subunit 1 OTOJNJRD VKOR1_HUMAN Biotransformations [13]
Vitamin K epoxide reductase complex subunit 1-like protein 1 OT7QSEWT VKORL_HUMAN Biotransformations [13]
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 Phytonadione (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Anisindione DM2C48U Moderate Antagonize the effect of Phytonadione when combined with Anisindione. Coagulation defect [3B10] [14]
Orlistat DMRJSP8 Minor Decreased absorption of Phytonadione caused by Orlistat. Obesity [5B80-5B81] [15]

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: 5286).
2 Phytonadione FDA Label
3 Jones KS, Bluck LJ, Wang LY, Coward WA: A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption. Eur J Clin Nutr. 2008 Nov;62(11):1273-81. doi: 10.1038/sj.ejcn.1602859. Epub 2007 Aug 1.
4 Soedirman JR, De Bruijn EA, Maes RA, Hanck A, Gruter J: Pharmacokinetics and tolerance of intravenous and intramuscular phylloquinone (vitamin K1) mixed micelles formulation. Br J Clin Pharmacol. 1996 Jun;41(6):517-23. doi: 10.1046/j.1365-2125.1996.03847.x.
5 Metabolism of vitamin K1 (phylloquinone) in man. Proc R Soc Med. 1977 Feb;70(2):93-6.
6 CA Prez Montilla, S Moroni, N Gonzlez, G Moscatelli, JM Altcheh, F Garca Bournissen: P38 Identification of Nifurtimox metabolites in urine of pediatric Chagas disease patients by UHPLC-MS/MS BMJ.
7 ?ie S, Trenk D, Guentert TW, Mosberg H, J?hnchen E: Disposition of vitamin K1 after intravenous and oral administration to subjects on phenprocoumon therapy International Journal of Pharmaceutics. 1988 Jun 15;48(1-3):223-230.
8 Quinone oxidoreductases and vitamin K metabolism. Vitam Horm. 2008;78:85-101.
9 Effects of CYP4F2 polymorphism on response to warfarin during induction phase: a prospective, open-label, observational cohort study. Clin Ther. 2012 Apr;34(4):811-23. doi: 10.1016/j.clinthera.2012.02.009. Epub 2012 Mar 13.
10 Vitamin K1 Inhibition of Renal Crystal Formation through Matrix Gla Protein in the Kidney. Kidney Blood Press Res. 2019;44(6):1392-1403. doi: 10.1159/000503300. Epub 2019 Oct 22.
11 Effect of cell differentiation for neuroblastoma by vitamin k analogs. Jpn J Clin Oncol. 2009 Apr;39(4):251-9. doi: 10.1093/jjco/hyp011. Epub 2009 Mar 8.
12 Specificity of increased des-gamma-carboxyprothrombin in hepatocellular carcinoma after vitamin K1 injection. J Hepatol. 1987 Aug;5(1):27-9. doi: 10.1016/s0168-8278(87)80057-0.
13 VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.
14 Howard PA, Hannaman KN "Warfarin resistance linked to enteral nutrition products." J Am Diet Assoc 85 (1985): 713-5. [PMID: 3998343]
15 Product Information. Xenical (orlistat). Roche Laboratories, Nutley, NJ.