You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePhylloquinone
Accession NumberDB01022  (APRD00464)
TypeSmall Molecule
GroupsApproved
Description

Phylloquinone is often called vitamin K1. It is a fat-soluble vitamin that is stable to air and moisture but decomposes in sunlight. It is found naturally in a wide variety of green plants. Phylloquinone is also an antidote for coumatetralyl. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation.

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedioneNot AvailableNot Available
2-Methyl-3-[(2e)-3,7,11,15-tetramethyl-2-hexadecenyl]naphthoquinoneNot AvailableNot Available
2-Methyl-3-phytyl-1,4-naphthochinonNot AvailableNot Available
2-Methyl-3-phytyl-1,4-naphthoquinoneNot AvailableNot Available
3-PhytylmenadioneNot AvailableNot Available
alpha-PhylloquinoneNot AvailableNot Available
FitomenadionaNot AvailableNot Available
PhyllochinonNot AvailableNot Available
PhyllochinonumNot AvailableNot Available
PhylloquinoneNot AvailableNot Available
Phythyl-menadionGermanNot Available
PhytomenadioneNot AvailableNot Available
PhytomenadionumNot AvailableNot Available
PhytonadioneNot AvailableNot Available
PhytonadionumNot AvailableNot Available
PhytylmenadioneNot AvailableNot Available
trans-PhylloquinoneNot AvailableNot Available
Vitamin K1Not AvailableNot Available
α-phylloquinoneNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mephytontablet5 mgoralKAISER FOUNDATION HOSPITALS2013-07-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralValeant Pharmaceuticals North America LLC2013-03-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralRebel Distributors Corp1955-09-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralPd Rx Pharmaceuticals, Inc.1955-09-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralPhysicians Total Care, Inc.2006-03-21Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralCardinal Health1955-09-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Mephytontablet5 mgoralCarilion Materials Management2013-03-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vitamin K1injection, emulsion2 mg/mLintramuscular; intravenous; subcutaneousHospira, Inc.1983-07-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vitamin K1injection, emulsion10 mg/mLintramuscular; intravenous; subcutaneousHospira, Inc.1983-07-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralAmphastar Pharmaceuticals, Inc.1988-03-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralAmphastar Pharmaceuticals, Inc.2003-04-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralGeneral Injectables & Vaccines, Inc2013-02-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralGeneral Injectables & Vaccines, Inc2014-01-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, solution1 mg/.5mLintramuscular; parenteral; subcutaneousGeneral Injectables & Vaccine, Inc2010-04-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vitamin K1injection, solution10 mg/mLintramuscular; intravenous; subcutaneousGeneral Injectables & Vaccines, Inc2010-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralGeneral Injectables & Vaccines, Inc2012-09-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vitamin K1injection, emulsion10 mg/mLintramuscular; intravenous; subcutaneousCardinal Health2011-08-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vitamin K1injection, emulsion2 mg/mLintramuscular; intravenous; subcutaneousCardinal Health2011-08-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralCardinal Health2003-04-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phytonadioneinjection, emulsion1 mg/.5mLparenteralInternational Medication Systems, Limited2003-04-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
Aqua-MephytonNot Available
KonakionNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number84-80-0
WeightAverage: 450.6957
Monoisotopic: 450.349780716
Chemical FormulaC31H46O2
InChI KeyMBWXNTAXLNYFJB-NKFFZRIASA-N
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
IUPAC Name
2-methyl-3-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]-1,4-dihydronaphthalene-1,4-dione
SMILES
CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=C(C=CC=C2)C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as vitamin k compounds. These are quinone lipids containing a methylated naphthoquinone ring structure, and vary in the aliphatic side chain attached at the 3-position.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassQuinone and hydroquinone lipids
Direct ParentVitamin K compounds
Alternative Parents
Substituents
  • Diterpenoid
  • Naphthoquinone
  • Naphthalene
  • Aryl ketone
  • Quinone
  • Benzenoid
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia.
PharmacodynamicsPhylloquinone is a vitamin, indicated in the treatment of coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity. Phylloquinone aqueous colloidal solution of vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X).
Mechanism of actionVitamin K is an essential cofactor for the gamma-carboxylase enzymes which catalyze the posttranslational gamma-carboxylation of glutamic acid residues in inactive hepatic precursors of coagulation factors II (prothrombin), VII, IX and X. Gamma-carboxylation converts these inactive precursors into active coagulation factors which are secreted by hepatocytes into the blood. Supplementing with Phylloquinone results in a relief of vitamin K deficiency symptoms which include easy bruisability, epistaxis, gastrointestinal bleeding, menorrhagia and hematuria.
AbsorptionOral phylloquinone is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phylloquinone is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationAlmost no free unmetabolized vitamin K appears in bile or urine.
Half lifeNot Available
ClearanceNot Available
ToxicityThe intravenous LD50 of phylloquinone in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Coagulation PhysiologicalSMP00586
Heparin Action PathwayDrug actionSMP00274
Streptokinase Action PathwayDrug actionSMP00282
Tranexamic Acid Action PathwayDrug actionSMP00287
Warfarin Action PathwayDrug actionSMP00268
Ardeparin Action PathwayDrug actionSMP00275
Lepirudin Action PathwayDrug actionSMP00278
Tenecteplase Action PathwayDrug actionSMP00283
Acenocoumarol Action PathwayDrug actionSMP00269
Argatroban Action PathwayDrug actionSMP00276
Ximelagatran Action PathwayDrug actionSMP00279
Urokinase Action PathwayDrug actionSMP00284
Dicumarol Action PathwayDrug actionSMP00270
Fondaparinux Action PathwayDrug actionSMP00273
Anistreplase Action PathwayDrug actionSMP00281
Aminocaproic Acid Action PathwayDrug actionSMP00286
Aprotinin Action PathwayDrug actionSMP00288
Dicoumarol Action PathwayDrug actionSMP00656
Enoxaparin Action PathwayDrug actionSMP00272
Bivalirudin Action PathwayDrug actionSMP00277
Alteplase Action PathwayDrug actionSMP00280
Reteplase Action PathwayDrug actionSMP00285
Phenprocoumon Action PathwayDrug actionSMP00271
Phenindione Action PathwayDrug actionSMP00655
Vitamin K MetabolismMetabolicSMP00464
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8941
Caco-2 permeable+0.7993
P-glycoprotein substrateSubstrate0.6643
P-glycoprotein inhibitor IInhibitor0.8581
P-glycoprotein inhibitor IIInhibitor0.9503
Renal organic cation transporterNon-inhibitor0.7232
CYP450 2C9 substrateNon-substrate0.7852
CYP450 2D6 substrateNon-substrate0.827
CYP450 3A4 substrateSubstrate0.6854
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateInhibitor0.8949
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateInhibitor0.8994
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7542
Ames testNon AMES toxic0.8945
CarcinogenicityNon-carcinogens0.9183
BiodegradationNot ready biodegradable0.9051
Rat acute toxicity1.1603 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5675
hERG inhibition (predictor II)Inhibitor0.5
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Hoffmann la roche inc
  • Aton pharma inc
  • Glaxosmithkline
  • International medication system
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, emulsionintramuscular; intravenous; subcutaneous10 mg/mL
Injection, emulsionintramuscular; intravenous; subcutaneous2 mg/mL
Injection, emulsionparenteral1 mg/.5mL
Injection, solutionintramuscular; intravenous; subcutaneous10 mg/mL
Injection, solutionintramuscular; parenteral; subcutaneous1 mg/.5mL
Tabletoral5 mg
Prices
Unit descriptionCostUnit
Phytonadione crystal111.13USD g
Phytonadione liquid66.0USD g
Vitamin k1 liquid35.0USD g
Mephyton 5 mg tablet5.95USD tablet
Vitamin K1 Pediatric 2 mg/ml4.79USD ml
Vitamin K1 10 mg/ml2.76USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point-20 °CPhysProp
boiling point142.5 °C at 1.00E-03 mm HgPhysProp
water solubilityInsoluble in waterNot Available
logP9.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.92e-05 mg/mLALOGPS
logP8.48ALOGPS
logP9.7ChemAxon
logS-6.9ALOGPS
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity142.96 m3·mol-1ChemAxon
Polarizability55.92 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraGC-MS
References
Synthesis Reference

Manfred Dorner, “Method of making vitamin K1.” U.S. Patent US5744624, issued June, 1964.

US5744624
General ReferenceNot Available
External Links
ATC CodesB02BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72 KB)
Interactions
Drug Interactions
Drug
WarfarinPhytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. Monitor for changes in prothrombin time if phytonadione intake (either via supplements or vitamin K-rich foods) is increased or decreased.
Food InteractionsNot Available

Targets

1. Vitamin K-dependent gamma-carboxylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Vitamin K-dependent gamma-carboxylase P38435 Details

References:

  1. Morris DP, Soute BA, Vermeer C, Stafford DW: Characterization of the purified vitamin K-dependent gamma-glutamyl carboxylase. J Biol Chem. 1993 Apr 25;268(12):8735-42. Pubmed
  2. Tuan RS: Vitamin K-dependent gamma-glutamyl carboxylase activity in the chick embryonic chorioallantoic membrane. J Biol Chem. 1979 Feb 25;254(4):1356-64. Pubmed
  3. Reedstrom CK, Suttie JW: Comparative distribution, metabolism, and utilization of phylloquinone and menaquinone-9 in rat liver. Proc Soc Exp Biol Med. 1995 Sep;209(4):403-9. Pubmed
  4. Tasatargil A, Cadir B, Dalaklioglu S, Yurdakonar E, Caglar S, Turkay C: Effects of vitamin K1 supplementation on vascular responsiveness and oxidative stress in a rat femoral osteotomy model. Cell Biochem Funct. 2007 Sep-Oct;25(5):485-90. Pubmed
  5. Olson RE: The function and metabolism of vitamin K. Annu Rev Nutr. 1984;4:281-337. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Osteocalcin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Osteocalcin P02818 Details

References:

  1. Sato Y, Tsuru T, Oizumi K, Kaji M: Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients. Am J Phys Med Rehabil. 1999 Jul-Aug;78(4):317-22. Pubmed
  2. Schurgers LJ, Dissel PE, Spronk HM, Soute BA, Dhore CR, Cleutjens JP, Vermeer C: Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90 Suppl 3:57-63. Pubmed
  3. Vermeer C, Wolf J, Craciun AM, Knapen MH: Bone markers during a 6-month space flight: effects of vitamin K supplementation. J Gravit Physiol. 1998 Oct;5(2):65-9. Pubmed
  4. Askim M: [Vitamin K in the Norwegian diet and osteoporosis] Tidsskr Nor Laegeforen. 2001 Sep 20;121(22):2614-6. Pubmed
  5. Kawana K, Takahashi M, Hoshino H, Kushida K: Circulating levels of vitamin K1, menaquinone-4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip fractures. Endocr Res. 2001 Aug;27(3):337-43. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on January 20, 2014 21:55